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10 Diabetes and Pregnancy Alyce M. Thomas Summary Diabetes mellitus is the most common complication in pregnancy, affecting nearly 8% of all pregnancies. Nearly 90% of women with diabetes develop the condition during pregnancy; diabetes in the other 10% antedated the pregnancy. Since the discovery of insulin, perinatal mortality rates for women with diabetes have decreased, however, infant morbidity remains higher than in the nondiabetes pregnant population. Diabetes in pregnancy can be classified as type 1 diabetes, type 2 diabetes, and gestational diabetes mellitus (GDM). Type 1 diabetes is characterized by insulin defi- ciency caused by autoimmune destruction of the pancreatic beta-cells. Type 2 diabetes is associated with insulin resistance and obesity rather than insulin deficiency. GDM is defined as glucose intolerance with onset or first recognition during pregnancy. The risk for maternal and fetal complications decreases if the woman is in optimal blood glucose control during pregnancy. Women with preexisting diabetes should receive preconceptional counseling during their childbearing years to achieve and maintain glycemic control and to address medical conditions that could affect the pregnancy. Self-management is the key to reducing the risks associated with diabetes and preg- nancy. For women with preexisting diabetes, these include medical nutrition therapy (MNT), insulin therapy, self-monitoring of blood glucose and ketones, and physical activity. Current nutrition recommendations for the treatment of diabetes may be used for pregnant women with type 1 diabetes and type 2 diabetes. MNT is the cornerstone of treatment for women with GDM. Most women with GDM can control their blood glucose by following a carbohydrate modified meal plan that also provides sufficient energy and nutrients to promote maternal and fetal health. Occasionally, medication may be added to maintain optimal blood glucose control. Breastfeeding is not contraindicated in GDM and should be encouraged. Women with GDM in a previous pregnancy are at risk of developing this condition in subsequent pregnancies and type 2 diabetes later in life. Women should be encouraged to develop healthy lifestyles to decrease their risk of developing diabetes-related conditions. Keywords: Preexisting diabetes, Gestational diabetes mellitus, Congenital anomaly, Insulin resistance, Insulin sensitivity, Normoglycemia From: Nutrition and Health: Handbook of Nutrition and Pregnancy Edited by: C.J. Lammi-Keefe, S.C. Couch, E.H. Philipson © Humana Press, Totowa, NJ 135

136 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy 10.1 INTRODUCTION Diabetes mellitus affects 20.8 million or 7% of the United States’ population, with 14.6 million diagnosed cases and 6.2 million unaware they have the disease [1]. It is the most common complication of pregnancy, estimated at 8% of all pregnancies or more than 200,000 cases annually [2]. Nearly 90% will develop diabetes during pregnancy [3]; the other 10% had diabetes that predated the pregnancy [2]. Although perinatal morbidity and mortality have decreased in the last 80 years, the prevalence of fetal complications in women with diabetes is higher than in women without diabetes. With intensive management and optimal glycemic control, prior to and throughout pregnancy, women with diabetes can reduce their risk of perinatal complications. 10.2 HISTORICAL BACKGROUND Before 1921, women with diabetes were advised to avoid pregnancy or to abort if they conceived because of adverse perinatal outcomes. If the pregnancies advanced to the stage of fetal viability, the infants were often stillborn or were born with major malfor- mations. Medical nutrition therapy was the primary method of management for pregnant women with diabetes prior to 1921; however, the diets were often severely restricted or nutritionally unbalanced. These dietary approaches varied from high carbohydrate-low protein, or high protein–high fat, to brief periods of starvation [4, 5]. Alcohol was often included because of its calming effect on the mother [6]. Although insulin injections revolutionized diabetes management, nutrition therapy remained virtually unchanged in the early years after its discovery. In 1937, Priscilla White, a physician at the Joslin Diabetes Center in Boston, Mass., developed a new meal plan, which consisted of 30 kcal/kg body weight, 1 g protein/kg actual body weight, and 180–250 g carbohydrate with the remainder as fat [7]. Other researchers used similar meal plans to achieve maternal blood glucose control [8, 9]. During the 1950–1960s, health care providers were concerned with the risk of macrosomia and hypertension in pregnancy. Weight gain and sodium were restricted to less than 15 lb and 2 g, respectively, in all pregnant women. After the publication of Maternal Nutrition and the Course of Pregnancy in 1970 [10], weight gain recommen- dations were increased to 22–30 lb, and the sodium restriction was discontinued. This comprehensive literature review found no evidence to support the restriction of weight or sodium in pregnancy. However, weight gain and sodium restrictions for pregnant women with diabetes continued until 1970, when the American Diabetes Association recommended the same regimen for pregnant women with diabetes as for the general pregnant population [11]. Today, pregnant women with and without diabetes follow the same weight gain recommendations. 10.3 CLASSIFICATION OF DIABETES The American Diabetes Association defines diabetes mellitus as a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both [12]. The main classification of diabetes mellitus is type 1, type 2, and GDM. Type 1 diabetes, formerly known as insulin-dependent or juvenile-onset diabetes, is characterized by autoimmune destruction of the pancreatic beta-cells and accounts

Chapter 10 / Diabetes and Pregnancy 137 for 5–10% of all diabetes cases. Type 1 diabetes requires exogenous insulin for survival and is diagnosed primarily in persons less than 30 years of age. Type 2 diabetes, which accounts for almost 90% of diabetes cases, was previously known as adult-onset or non-insulin dependent diabetes. Insulin resistance rather than insulin deficiency and obesity are associated with type 2 diabetes. GDM is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. The definition applies if medication or MNT is used in treatment or the condition per- sists after pregnancy. It does not exclude the possibility that the diabetes may have existed prior to pregnancy. Diabetes in pregnancy is classified whether the condition predated (type 1 diabetes or type 2 diabetes) or was diagnosed during pregnancy (GDM). Other classifications have been used to identify risk factors associated with diabetes in pregnancy, including age of onset, presence of preexisting complications and degree of metabolic control [13, 14]. 10.4 PREEXISTING DIABETES 10.4.1 Pathophysiology of Normal Pregnancy During pregnancy, the fetus receives nutrients from across the placenta, including glucose, amino acids, and fatty acids via either active transport or facilitated diffusion. In the first trimester, maternal glycogen storage and endogenous glucose production increase. Pregnancy hormones (human placental lactogen and cortisol), estrogen, pro- gesterone, and the constant fetal demand of glucose lower fasting maternal blood glu- cose levels [15, 16]. The maternal appetite is stimulated resulting in consumption of additional calories. Fasting and postprandial glucose levels rise in response to the extra glucose required for fetal growth. Elevated hormonal levels increase insulin resistance and the beta-cells produce and secrete additional insulin as glucose is transported across the placenta. Insulin resistance peaks by the latter part of the third trimester, which is characterized by a three-fold increase in insulin production and secretion. After delivery, insulin production returns to prepregnancy levels. Other hormones thought to affect insulin resistance include leptin, insulin-like growth factors, relaxin, and adiponectin [17–19]. Maternal insulin does not cross the placental barrier unless bound to insulin immunoglobulins. Fat is deposited and stored primarily in early pregnancy, then mobilized in the third trimester as fetal energy demands increase. Free fatty acids have been shown to contribute to insulin resistance in late pregnancy [20]. 10.4.1.1 Type 1 Diabetes Insulin is necessary for carbohydrate, fat, and protein metabolism. In type 1 diabetes, blood glucose levels remain elevated as insulin deficiency and the rise in free fatty acids lead to the formation of ketones and beta-hydroxybutyrate. The risk of diabetic ketoaci- dosis increases in the absence or lack of insulin. Women in optimal glycemic control may experience increased insulin sensitivity and decreased insulin requirements in the first trimester. During the second and third trimesters, elevated hormonal levels increase insulin resistance and additional insulin is necessary to maintain normal maternal glyc- emic levels and decrease fetal complications.

138 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy 10.4.1.2 Type 2 Diabetes Type 2 diabetes is associated with impaired insulin secretion, insulin insensitivity, and pancreatic beta-cell dysfunction. Women with type 2 diabetes tend to be older, heavier, and have higher insulin resistance than women with type 1 diabetes. The fetal pancreas is stimulated to secrete additional insulin in the presence of excessive glucose. Higher fetal insulin levels may result in macrosomic growth. Exogenous insulin may be neces- sary to maintain normoglycemia as insulin deficiency and insulin resistance increase. 10.4.2 Complications Associated with Preexisting Diabetes Complications associated with diabetes can adversely affect both the woman and fetus. The incidence of fetal complications is correlated with maternal glycemic control and the trimester of pregnancy. 10.4.2.1 Fetal Congenital malformations and spontaneous abortions are associated with maternal hyperglycemia in the first 12 weeks of gestation. The central nervous system, heart, lungs, gastrointestinal tract, kidneys, urinary tract, skeleton, and placenta are all vulner- able to adverse effects (Table 10.1) [21–23]. The frequency and severity of complica- tions decrease if maternal normoglycemia is maintained throughout pregnancy. Second- and third-trimester fetal complications include macrosomia, neonatal hypoglycemia, neonatal hypocalcemia, hyperbilirubinemia, polycythemia, respiratory distress syndrome, preterm delivery, and stillbirth. With the exception of stillbirth, other complications are more closely associated with infant morbidity than mortality. Macrosomia is the most common complication associated with diabetes and pregnancy, estimated at 20–45%, depending on the population [24, 25]. The definition of macro- somia varies and ranges from 4,000 to 4,500 g [26]. Macrosomia is thought to occur if maternal glycemic levels are elevated in the third trimester. Pedersen hypothesized that maternal hyperglycemia leads to fetal hyperglycemia, which stimulates the fetal pancreas to produce excessive insulin and results in excess growth [27]. Macrosomic infants have disproportional large fetal trunks in relation to their head size, thereby increasing the risk of difficult delivery, shoulder dystocia, brachial plexus palsy, or facial nerve injury. Neonatal hypoglycemia is a fetal serum glycemic level <35 g/dl in the first 12 h of life. Maternal glucose transport abruptly ceases when the umbilical cord is clamped. If fetal hyperinsulinemia continues, the infant will experience a rapid decrease in glycemic levels. The preferred method of treatment is oral feeding, preferably with breast milk, and frequent blood glucose monitoring within the first 4–6 h of life. Respiratory distress syndrome is caused by a deficiency of surfactant, necessary for fetal lung maturity. Neonatal hypocalcemia is serum calcium <7 mg/dl. Hyperbilirubinemia occurs when the serum bilirubin level of the neonate >13 mg/dl. Polycythemia, which is a hematocrit >65% at delivery, could lead to perinatal asphyxia. The risk of these conditions decreases if the mother maintains optimal glycemic control throughout pregnancy. Advances in diabetes research and management have led to decreased risks of stillbirth in infants born to women with preexisting diabetes, though it remains higher than in the general pregnant population. Maternal vascular complications, poor blood glucose control, and inadequate or no prenatal care are associated with higher rates of stillbirths in women with diabetes prior to pregnancy.

Chapter 10 / Diabetes and Pregnancy 139 Table 10.1 Congenital Anomalies Associated with Preexisting Diabetes and Pregnancy Central Nervous System • Neural tube defects (e.g., anencephaly, spina bifida, hydrocephalus) • Microcephaly • Dandy-Walker complex Cardiovascular • Coarctation • Transportation of great vessels • Truncus arteriosus • Aortic stenosis Gastrointestinal • Duodenal atresia • Anorectal atresia • Gastroschisis Genitourinary • Renal agenesis • Hydronephosis • Cystic kidneys • Anal/rectal atresia Skeletal • Caudal regression syndrome From [21–23] 10.4.2.2 Maternal Preconceptional maternal complications include nephropathy, neuropathy, retinopa- thy, hypertension, and diabetic ketoacidosis. Diabetic nephropathy is associated with other complications including preeclampsia, anemia, intrauterine growth restriction, fetal demise, and preterm delivery [28, 29]. If maternal glycemic levels are in optimal control before conception, the severity of complications and further renal deterioration during and after pregnancy are reduced. Pregnancy itself is not a risk factor for the development or progression of diabetic neuropathy. Gastroparesis, a condition in which the stomach’s ability to empty its contents is impaired because of a possible disrup- tion of nerve stimulation to the intestine, occurs more often in type 1 diabetes. Women with gastroparesis may experience nausea, vomiting abdominal discomfort and diffi- culty in controlling blood glucose. Few studies have been published on gastroparesis and pregnancy. One case report noted severe and intractable vomiting in two women with gastroparesis resulting in fetal demise in one of the pregnancies [30]. The effect of pregnancy on diabetic retinopathy depends on the severity of the condition, whether proteinuria or hypertension are present. In most cases, background retinopathy regresses after delivery. Proliferative retinopathy may progress if the condition was untreated prior to pregnancy [31, 32]. Laser photocoagulation is contraindicated in pregnancy, and the woman is advised to delay conception to avoid further eye damage. Obesity is a risk factor for hypertension and is primarily associated with type 2 diabetes [3, 34]. Diabetic ketoacidosis occurs more rapidly in pregnancy than in nonpregnancy because

140 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy of increased insulin resistance and accelerated starvation ketosis. Factors that precipi- tate diabetic ketoacidosis include hyperemesis, gastroparesis, insulin pump failure, and certain medications, such as steroids [35]. Complications that develop during pregnancy include hypertensive disorders, poly- hydramnios, preterm delivery, and cesarean section. Poor blood glucose control in early pregnancy is associated with the development of preeclampsia and pregnancy-induced hypertension [35]. Although the etiology of polyhydramnios (excessive amniotic fluid) is not well understood, it is associated with suboptimal blood glucose control. Macrosomia may warrant preterm or cesarean delivery. 10.5 MEDICAL NUTRITION THERAPY There are no specific dietary guidelines for pregnant women with preexisting diabetes. Current guidelines for nutrition recommendations in pregnant women without diabetes may be used for pregnant women with type 1 diabetes and type 2 diabetes. Individualizing the meal plan is the key to providing adequate calories and nutrients to the woman and fetus. The meal plan works concurrently with the insulin regimen to achieve target blood glucose levels. The goals of MNT for pregnancy and diabetes are (1) to provide adequate nutrients for maternal-fetal nutrition, (2) to provide sufficient calories for appropriate weight gain, and (3) to achieve and maintain optimal glycemic control. 10.5.1 Weight Gain Weight gain recommendations are based on the 1990 Institute of Medicine’s pub- lication, Nutrition during Pregnancy, according to the women’s prepregnancy BMI (Table 10.2) [37]. The prepregnancy BMI and the amount of weight gained dur- ing pregnancy are two factors affecting perinatal outcome. Weight gain below the Institute of Medicine’s recommendations is associated with low birth weight and small-for-gestational-age infants. Excessive weight gain may lead to macrosomia, cesarean section, and unnecessary postpartum weight retention. Overweight women with diabetes need to gain minimum weight to decrease the risk of macrosomia. 10.5.2 Energy Requirements The estimated energy requirements (EER) during pregnancy are based on the 2002 Dietary Reference Intakes [38]. The EER for pregnancy are: Table 10.2 Recommended Ranges of Total Weight Gain for Pregnant Women Prepregnancy BMI Recommended weight gain Rate of gain/week (2nd and 3rd trimesters) Underweight (<19.8) 28–40 lb (12.7–18.2 kg) Normal weight (19.8–26) 25–35 lb (11.2–15.9 kg) 1.5 lb (0.7 kg) Overweight (26.0–29) 15–25 lb (6.8–11.3 kg) 1 lb (0.5 kg) Obese (>29) 15 lb (6.8 kg) 0.6 lb (0.3 kg) Twin gestation 35–45 lb (15.9–20.5 kg) Individualize Triplet gestation 45–55 lb (20.5–25 kg) 1 ½ lb (0.7 kg) 2–2 ½ lb (0.9–1.1 kg) From [37]

Chapter 10 / Diabetes and Pregnancy 141 ● First trimester: adult EER for women (no calorie increase) ● Second trimester: adult EER for women +160 kcal (8 kcal/week × 20 weeks) + 180 kcal ● Third trimester: adult EER for women +272 kcal (8 kcal/week × 34 weeks) + 180 kcal The EER for adult women is based on age, height, weight, and physical activity level, which is higher than the previous recommendation of 300 extra kilocalories daily, begin- ning in the second trimester. Adequate calories are required to avoid starvation ketosis and ketoacidosis. A comprehensive nutrition history/questionnaire, food record/diary and blood glucose records, and regular monitoring of weight are used to develop indi- vidualized meal plans. Fluctuating blood glucose levels may necessitate frequent adjust- ments in the meal plan. 10.5.3 Macronutrients The requirement for protein is 71 g/day or 1.1 g/kg/day for women over 18 years of age [38]. High-fat diets are not recommended and saturated fats are limited to less than 10% of total calories from fat. The Recommended Daily Allowance for carbohydrate intake in pregnancy is 175 g/ day to ensure sufficient glucose for fetal brain growth and development, estimated to be 33 g/day [38]. While there is no carbohydrate restriction for women with preexisting diabetes, adjustments may be necessary to maintain normoglycemia. 10.5.4 Micronutrients Calcium, vitamin D, magnesium, iron, and folic acid are frequently consumed in inadequate amounts in pregnancy [39]. The fetus requires calcium throughout preg- nancy, which is mostly deposited in the skeletal tissues in the third trimester. Vitamin D is required for calcium absorption and deposition in the fetal skeleton. Women with inadequate vitamin D intakes or limited sunlight exposure are at risk for vitamin D defi- ciency, increasing the risk of neonatal rickets. Magnesium deficiency may be associated with preeclampsia [40]. A low dose supplementation of 30 mg iron/day is recommended beginning in the second trimester. Folate is necessary for DNA synthesis and maternal and fetal cell proliferation. Folate deficiency is associated with maternal megaloblastic anemia, neural tube defects, spontaneous abortions, and low birth weight [41]. Folic acid supplementation should begin prior to conception and continue throughout pregnancy. 10.5.5 Nonnutritive Sweeteners Five nonnutritive sweeteners are approved for use in pregnancy when used within the Acceptable Daily Intakes: saccharin, aspartame, acesulfame potassium, sucralose, and neotame [42]. 10.6 MEAL-PLANNING APPROACHES Various meal-planning approaches are used in diabetes management. The meal plan followed prior to conception may need only minor adjustments to account for fetal growth. Women with no previous MNT will need more intensive self-management edu- cation. The appropriate meal-planning tool selected depends on the woman’s ability and motivation to follow the plan. Meal-planning approaches include menus, plate method, Food Guide Pyramid, or Exchange Lists for Meal Planning [43]. Carbohydrate counting is used more often today as clients learn the importance of employing amounts and food

142 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy sources of carbohydrates, label reading, and food records. Pattern management, calcu- lating insulin-to-carbohydrate ratios and correction factors are advanced forms of meal planning [43]. 10.7 MEDICATIONS Exogenous insulin therapy is used for women with preexisting diabetes. Although certain oral antidiabetic agents are used with GDM, there are limited studies on their use in pregnancy with type 2 diabetes. Human insulin is recommended in pregnancy, as it is less allergenic and has a quicker absorption rate than animal-based insulin. Rapid-acting insulin analogs (Lispro, Aspart) are frequently used in pregnancy, yielding results similar to short-acting insulin [44–47]. Glargine and Detemir are long-acting, peakless insulin analogs. No clinical studies have been conducted on their use during pregnancy, though case reports have not shown teratogenic effects. Injectable therapies that have not demonstrated safety in pregnancy include incretin mimetic hormones (Pramlintide and Exenatide). Multiple daily injections of rapid-acting insulin or short-acting insulin with an inter- mediate acting are the most frequently used insulin administrations in pregnancy (Table 10.3). Women who were on a fixed dose of insulin before conception are often switched to multiple daily injections because of the need for frequent insulin adjustments. A common insulin regimen is rapid-acting or short-acting insulin before breakfast and dinner, or before each meal and intermediate-acting before breakfast and at bedtime. Intermediate-acting insulin is not usually injected before dinner because of possible nocturnal hypoglycemia. Insulin requirements change during pregnancy as fetal growth continues and insulin resistance increases. First-trimester insulin regimen varies but is usually 0.7–0.8 units/kg actual body weight/day; second trimester: 0.8–1 unit/kg actual body weight/day; and 0.9–1.2 units/kg actual body weight/day in the third trimester. [35]. The requirements for obese women may be higher (1.5–2 units/kg actual body weight/day). Insulin injection devices include syringes, pens, and continuous subcutaneous insulin pumps (insulin pump therapy). Pump therapy requires rapid-acting insulin with 50–60% of the dose as basal for continuous insulin and 40–50% as boluses before meals and snacks. Advantages to the insulin pump are flexibility with lifestyle and meal times, and improved glucose control. The disadvantages include cost, risk of interruption in insulin delivery or infection at the infusion site. Table 10.3 Human Insulin Insulin type Onset (h) Peak action (h) Duration (h) Rapid-acting (Lispro, Aspart, Glulisine) 5–15 min 1–2 4–6 Short-acting (Regular) 0.5–1 2–4 6–10 Intermediate-acting (NPH) 1–2 4–8 10–18 (long-acting) Long-acting (Glargine, Detemir) 1–2 Peakless Up to 24 From Messing C (ed) (2006) The art and science of diabetes self-management education: a desk reference for healthcare professionals. American Association of Diabetes Educators, Chicago, Ill., p 38

Chapter 10 / Diabetes and Pregnancy 143 10.8 SELF-MANAGEMENT TOOLS Medical nutrition therapy and insulin therapy are only two of the components for suc- cessful self-management. Food records will assist the registered dietitian to adjust the meal plan, when necessary. Other tools include sick-day rules, self-monitoring of blood glucose and ketones, and physical activity. 10.8.1 Sick-Day Rules Hypoglycemia is a concern if the woman is ill and consuming inadequate calories. All pregnant women with preexisting diabetes should be aware of hypoglycemia symptoms, which range from sweating, blurred vision, nervousness, anxiety, headache, weakness, or in severe cases, seizures or unconsciousness. The treatment for hypoglycemia depends on the severity of the symptoms. Mild-to-moderate symptoms are treated with 15 g of carbo- hydrate if the blood glucose level is <60 mg/dl. This is repeated at 15 minutes later if the blood glucose level remains <60 mg/dl. If severe hypoglycemia occurs, either glucagons or intravenous glucose is used [48]. 10.8.2 Self-Monitoring Monitoring provides a necessary tool for adjusting food, medication, and physical activ- ity in diabetes management. Women with preexisting diabetes need to monitor their blood glucose levels, using a glucose meter before and after meals. The blood glucose goals for diabetes and pregnancy are in Table 10.4. Urine ketone monitoring of the first morning specimen may be necessary if energy intake or weight gain is inadequate. Glycosylated hemoglobin (HbA1C), while not a self-monitoring tool, is used clinically to assess blood glucose levels in the preceding 6–8 weeks to determine metabolic control and treatment. 10.8.3 Physical Activity No evidence has shown any beneficial effect of physical activity on glycemic control in women with type 1 diabetes. Unless contraindicated, women who were physically active before pregnancy are encouraged to continue, although the type and duration may change. Contraindications to exercising with diabetes in pregnancy include glycemic levels <100 mg/dl or >250 mg/dl [49]. Table 10.4 Glycemic Goals in Diabetes and Pregnancy Fasting mg/dl mmol/l Preprandial 1 h postprandial 60–95 3.3–5.2 2 h postprandial 60–115 3.3–6.4 Nocturnal <140 <8.1 <120 <6.6 60–135 3.3–5.6 From [35]

144 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy 10.9 POSTPARTUM Insulin requirements usually decrease after delivery and it is not uncommon for the woman to forego insulin for the first 1–2 days after delivery. Insulin adjustments are necessary to prevent hypoglycemia. There are no contraindications to lactation for the woman with diabetes, and women should be encouraged to breastfeed. The meal plan is adjusted to include additional snacks to avoid hypoglycemia, which may be more frequent during lactation. Women with type 2 diabetes and choosing to breastfeed are advised to continue insulin therapy for the duration of lactation [35, 50]. Oral antidiabetic agents may resume once breastfeed- ing is terminated or if the woman chooses to formula feed her infant. Family planning is an important topic to discuss with the woman with preexisting diabetes. The use of contraceptive agents will depend on whether cardiovascular disease is present [51]. Low-dose combinations of progestin and estrogen or progestin-only oral contraceptive agents are recommended for women with hyperlipidemia. Intrauterine devices and barrier methods do not affect blood glucose levels. 10.10 PRECONCEPTIONAL COUNSELING Preconception counseling is essential for all women with preexisting diabetes in their childbearing years. Women with type 1 diabetes or type 2 diabetes should delay preg- nancy until their glycosylated hemoglobin levels are <1% above the normal range prior to conception to decrease the risk of adverse perinatal outcomes [52]. Preconceptional care includes a complete physical examination to identify and treat any preexisting diabetes-related or other medical condition, an assessment of her nutritional status, and self-management education, including psychosocial assessment. A discussion of finances is also important because of the additional expense of more frequent testing or diabetes supplies. Although all women with preexisting diabetes should receive preconceptional counseling, this often does not occur. Recent studies have shown that women with type 2 diabetes are not referred as frequently for preconceptional counseling as their type 1 diabetes counterparts [35, 53–56]. McElduff et al. found that only 12% of women with type 2 diabetes received preconceptional care compared with 27.8% of women with type 2 diabetes [54]. In another study, women with type 2 diabetes had a higher incidence of poor perinatal outcome, including fetal demise, congeni- tal anomalies, and difficult deliveries than women with type 1 diabetes [53]. One reason for this higher prevalence of complications is the misconception that type 2 diabetes is not as severe a condition as type 1 diabetes. This myth must be dispelled and strategies developed, including intensive diabetes self-management, to improve outcomes. 10.11 GESTATIONAL DIABETES MELLITUS It is estimated that 90% of cases of diabetes in pregnancy is GDM [35]. This includes women with possible undiagnosed type 1 or type 2 diabetes prior to conception. For most women who develop diabetes during pregnancy, normoglycemia returns following delivery.

Chapter 10 / Diabetes and Pregnancy 145 10.11.1 Pathophysiology GDM is similar to type 2 diabetes, as it is associated with insulin resistance and insen- sitivity. The exact mechanism responsible for the development of GDM is not fully under- stood; however, pancreatic beta-cell dysfunction may be responsible. As hormonal levels continue to rise in the second and third trimesters, beta-cells are unable to produce or secrete sufficient insulin for glucose regulation. Fasting blood glucose levels are elevated as insulin deficiency and resistance increase. Delayed insulin response, insulin resistance, and placental hormonal antagonism are responsible for postprandial glucose excursions. Human placental lactogen and cortisol block insulin receptors, which creates a deficiency in circulating insulin production, and results in increased glucose intolerance. In nor- mal pregnancy, the beta-cells compensate by increasing insulin secretion; in GDM the decreased insulin response will result in elevated glycemic levels [57]. 10.11.2 Complications Maternal risks for gestational diabetes include hypertension, higher rates of caesarean sections and preterm deliveries [3, 58]. Congenital anomalies are rare in gestational dia- betes. The exception would be the woman diagnosed with gestational diabetes early in the first trimester and in poor blood glucose control. Macrosomia is the most common complication in gestational diabetes. Other complications include neonatal hypoglyc- emia, neonatal hypocalcemia, neonatal hyperbilirubinemia, and polycythemia. The risk for respiratory distress syndrome decreases if delivery occurs at term. 10.11.3 Risk Factors for Gestational Diabetes Mellitus There is considerable controversy over the screening and diagnosis of GDM. The American Diabetes Association recommends assessing all pregnant women for risk of GDM at their first prenatal visit. Risk factors for diabetes are categorized as low, aver- age, and high [3]. Women in the low risk category must meet all of the following criteria and require. No further screening: ● Less than 25 years of age ● Normal BMI ● No first-degree family history of diabetes ● No history of glucose intolerance ● No history of poor perinatal outcome ● Not a member of a group with a high prevalence of diabetes, which includes those of Afri- can, Hispanic, Asian, Pacific Islander, or Native American descent Women at high risk must meet one or more of the following criteria: ● Obese ● Previous history of GDM ● Glycosuria ● Strong family history of diabetes ● Member of an ethnic group with a high prevalence of diabetes (see above) High-risk women are screened at their first prenatal visit. The test is repeated between 24 and 28 weeks of gestation if the initial screen was normal.

146 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy Women at average risk are those not at low or high risk. They are screened for GDM at 24–28 weeks of gestation. 10.11.4 Screening and Diagnosis of Gestational Diabetes Mellitus Two approaches are used to screen and diagnose for GDM, the two-step and the one- step method [3]. The two-step method is used primarily in the United States. The first step is the oral glucose challenge test (OGCT). A solution containing 50 g glucose is consumed, and the plasma glucose level is checked 1 h later. If the test is ≥140 mg/dl, the second step, the oral glucose tolerance test (OGTT) is administered after 3 days of unrestricted carbohydrates (at least 150 g/day) and unlimited physical activity. The woman fasts for at least 8 h the night before the test. Blood is drawn for a fasting glucose level, followed by 100 g of glucose solution given orally and redrawn at 1, 2, and 3 h. The oral glucose tolerance test is discontinued if the fasting glucose is ≥126 mg/dl or a random glucose is ≥ 200 mg/dl. GDM is diagnosed if at least two of the values exceed the Carpenter and Coustan criteria (see Table 10.5). The second method eliminates the 50 g OGCT. The one-step approach uses a 75-g glucose solution as the OGTT and the blood is drawn at fasting, 1 h, and 2 h. The criteria for the diagnosis of GDM are the same as the 3-h oral glucose tolerance test (Table 10.5). This method is used by the World Health Organization, but may also be more cost-effective in populations at high risk for GDM. One abnormal value on the oral glucose tolerance test is not a diagnosis for GDM; however, it may indicate adverse perinatal outcome compared to women with normal results [59]. 10.11.5 Management of Gestational Diabetes There are no universal guidelines in the management of GDM. A recent Australian randomized, controlled trial of 1,000 women with gestational diabetes showed that treat- ing women with GDM reduced the risk of perinatal complications [60]. In this study by Crowther et al., the intervention group received MNT, self-monitored their blood glu- cose levels, and if indicated received insulin therapy. Perinatal complications were 1% in the intervention group and 4% in the group receiving routine care. 10.11.5.1 Medical Nutrition Therapy MNT is the cornerstone of treatment in the management of GDM. The American Diabetes Association and the American College of Obstetricians and Gynecologists recommend nutritional counseling by a registered dietitian and an individualized meal plan [3, 58]. The American Dietetic Association’s evidence-based Nutrition Practice Guidelines have identified the following MNT goals for GDM: (1) to achieve and main- Table 10.5 Diagnostic Criteria for Gestational Diabetes Mellitus Fasting 100 g OGTT 75 g OGTT 1h 2h 95 mg/dl (5.2 mmol/l) 95 mg/dl (5.2 mmol/l) 3h 180 mg/dl (10 mmol/l) 180 mg/dl (10 mmol/l) 155 mg/dl (8.6 mmol/l) 155 mg/dl (8.6 mmol/l) 140 mg/dl (8.1 mmol/l) From [12], OGTT: Oral Glucose Tolerance Test

Chapter 10 / Diabetes and Pregnancy 147 tain normoglycemia, (2) to provide sufficient calories to promote appropriate weight gain and avoid maternal ketosis, and (3) to provide adequate nutrients for maternal and fetal health [61]. The American Dietetic Association provides an algorithm for MNT for GDM (Fig. 10.1). The Institute of Medicine’s recommendations are used to determine the appropriate weight gain for women with gestational diabetes (38). The EER are the same for pregnant women without diabetes. Monitoring weight gain, and reviewing blood glucose, food and if necessary, ketone records are other useful tools to determine diet adequacy. The Dietary Reference Intakes do not provide a recommendation EER for obese women. Several studies used various calorie restrictions to determine minimum energy requirements, while avoiding ketonuria and ketonemia. A minimum of 1,700–1,800 kcal/ day appears to improve glucose control without increasing ketone levels [3, 58, 61]. Fig. 10.1. Algorithm for MNT. (From [61], used with permission)

148 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy Carbohydrates are the main contributors of postprandial glucose excursions in GDM. The amount, source, and distribution of carbohydrates are determined in conjunction with blood glucose monitoring. The nutrition practice guidelines recommend restricting the carbohydrate content to 40–45% of total calories, but not less than the Dietary Refer- ence Intakes recommendation of 175 g/day to achieve blood glucose goals. Carbohydrate sources include whole grains, dried beans and peas, and lentils, which are more nutrient dense and have a lower glycemic response than processed foods, such as instant products (e.g., cereals, rice, and potatoes) or highly refined grain products. The distribution of carbohydrates into three meals and two to four snacks will help control postmeal blood glucose levels [61]. Carbohydrate intake is more restricted at breakfast than at other meals, as hormonal levels are higher in the morning. The total amount of carbohydrates at breakfast can range from 15 to 45g. Breakfast cereals, milk, and fruit may need to be consumed at other meals or snacks. Carbohydrate distribution at lunch and dinner is usually 30–45g or higher, depending on postprandial glycemic levels. The distribution of snacks is 15–45g, with a smaller snack in the morning. An evening snack will help avoid overnight starvation ketosis. Protein is not associated with postprandial glycemic elevations. The protein intake increases to 25–25% of total calories as the carbohydrate level is reduced, and usually exceeds the Dietary Reference Intakes of 71 g/day or 1.1 g/kg/day [61]. Fat makes up 35–40% of the total calories, with the majority as monosaturated and polyunsaturated fats [62, 63]. 10.11.5.2 Self-Management Tools Self-management is important for improving perinatal outcome in GDM. Other self- management tools in addition to MNT include self-monitoring of blood glucose and ketone levels, physical activity, and the initiation of medication, when necessary. 10.11.5.2.1 Self-Monitoring of Blood Glucose. Although the American Diabetes Association and the American College of Obstetricians and Gynecologists recommend daily monitoring of blood glucose levels in GDM, there is no consensus on frequency of testing [3, 58]. Research has indicated fewer complications (macrosomia, cesarean section, birth injury, neonatal hypoglycemia) with daily use of blood glucose meters than with weekly laboratory testing of fasting and postprandial levels [3]. While preprandial testing is recommended with preexisting diabetes, postprandial monitoring of blood glucose levels have yielded better outcomes, e.g., decrease in fetal macrosomia, large-for-gestational-age infants, in GDM [64]. Optimal testing times for blood glucose levels have not been estab- lished. Studies comparing 1-h and 2-h postprandial monitoring have shown conflicting results [65, 66]. (See Table 10.4 for target blood glucose levels.) 10.11.5.2.2 Ketone Monitoring. In an effort to avoid insulin injections, women may consume fewer calories than recommended; however, this practice may increase their risk of developing ketones. Rizzo et al. found decreased intelligence scores correlat- ed with ketonemia [67]. Urine ketone monitoring is not widely used in practice because it does not reflect the level of ketonemia, but it may be useful in detecting inadequate calorie or carbohydrate intake [3, 61]. 10.11.5.2.3 Physical Activity. Physical activity may have a positive effect on glycemic control by increasing insulin sensitivity and obviating the need for insulin therapy [58, 68, 69]. Low-impact aerobics, such as walking, stair climbing, or swimming are acceptable. The activity should be performed after meals to improve glycemic levels. Pregnant women with diabetes should seek medical approval prior to beginning an exercise program.

Chapter 10 / Diabetes and Pregnancy 149 10.11.5.2.4 Medication. Insulin therapy is used concurrently with MNT if normogly- cemia is not consistently maintained with diet only. There is no consensus of opinion as to when insulin therapy should be instituted. The nutrition practice guidelines recom- mend beginning insulin therapy 2 weeks after MNT is implemented [61]. The American Diabetes Association and the American College of Obstetricians and Gynecologists use different glycemic cut-offs for initiating insulin (Table 10.6). Ultrasound measurement of the fetal abdominal circumference to determine macrosomic growth is also used to determine initiatiation of insulin therapy [70]. Human-based insulin is preferred over animal-based because it is less allergenic. The type, dosage, and regimen vary but are usually a combination of short-acting and intermedi- ate-acting insulin. Calculation of the starting dose uses an approach that is similar to that employed for preexisting diabetes, and self-monitoring of blood glucose is used to guide the dose and timing of the regimen and subsequent adjustments. Insulin analogs are not yet approved by the Food and Drug Administration for use in GDM. Studies using insulin Lispro and insulin Aspart in GDM were not associated with adverse effects [71, 72]. Prior to 2000, oral antidiabetic agents were contraindicated during pregnancy. First- generation sulfonylureas crossed the placenta and were thought to cause fetal hyper- insulinemia or teratogenicity. A randomized trial by Langer et al. in which Glyburide, a second-generation sulfonylurea, was compared to insulin and reported no difference in the incidence of maternal or fetal complications, including preeclampsia, cesarean sections, macrosomia, or fetal anomalies [73]. Glyburide was also not detected in the cord serum. Four percent of the women on Glyburide did require insulin therapy. The American Diabetes Association and the American College of Obstetricians and Gynecolo- gists have not recommended Glyburide in pregnancy, although both organizations have acknowledged its use in controlling blood glucose levels in GDM. The advantages of Glyburide in pregnancy, according to healthcare providers who advocate its use, are that it is cost-effective, non-invasive, and may result in better compliance than insulin injec- tions [74]. Recent research in Glyburide therapy use in pregnancy demonstrated a failure rate of 12–20% [75, 76]. Women with high fasting blood glucose levels (≥110 mg/dl) were more likely to be switched to insulin therapy [76]. Further research is needed to determine the safety of other oral antidiabetic agents in pregnancy. 10.11.6 Postpartum Women with GDM are at increased risk for developing type 2 diabetes after preg- nancy and should be screened 6–12 weeks postpartum [3, 58]. The American Diabetes Association recommends a 75-g, 2-h oral glucose tolerance test to identify women with possible undiagnosed diabetes before conception, impaired glucose tolerance, or risk for Table 10.6 Criteria for Initiating Insulin in GDM Fasting American Diabetes American College of 1 h postprandial Association Obstetricians and Gynecologists 2 h postprandial ≤ 105 mg/dl (5.8 mmol/l) < 95 mg/dl (5.2 mmol/l) ≤ 155 mg/dl (8.6 mmol/l) < 130 mg/dl (7.2 mmol/l) ≤ 130 mg/dl (7.2 mmol/l) < 120 (6.6 mmol/l) From [3, 58]

150 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy Table 10.7 Criteria for Diagnosis of Diabetes Mellitus using a 75 g OGTT Impaired fasting Impaired glucose Diabetes mellitus Normal values glucose mg/dl tolerance mg/dl mg/dl (mmol/l) mg/dl (mmol/l) (mmol/l) (mmol/l) Fasting plasma <100 mg/dl ≥100 to <126 mg/dl <100 mg/dl (< ≥ 126 mg/dl (≥ 7.0 mmol/l) glucose (5.6 mmol/l) (≥ 5.6–7.8 mmol/ 5.6 mmol/l) ≥200 mg/dl l) 11.8 mmol/l) 75 g OGTT <140 mg/dl <140 mg/dl ≥140 to <200 mg/ (7.8 mmol/l) (7.8 mmol/l) dl (≥ 7.8– 11.1 mmol/l) From American Diabetes Association (2004) Screening for type 2 diabetes. Diabetes Care 27(Suppl 1): S11–S14, OGTT: Oral Glucose Tolerance Test future diabetes (Table 10.7) [3]. If the oral glucose tolerance test is normal at 6–12 weeks postpartum, the woman should be reassessed every 3 years. Women with impaired fasting glucose or impaired glucose tolerance need to be tested annually for diabetes. Breastfeeding, unless contraindicated, is recommended for women with GDM [3]. Lactation may improve glucose control, mobilize fat stores, promote weight loss, and protect against future risk of developing diabetes [36, 77]. Gradual weight loss (1–2 kg/ month) is encouraged. Oral contraceptive use in women with previous GDM is associated with thromboem- bolism, myocardium infarction, stroke, and increased insulin resistance [78, 79]. If an oral contraceptive agent is desired, a low potency dose of progestin and estrogen is prescribed to minimize the adverse effects of glucose intolerance and increased serum lipids [51]. Women with previous histories of GDM are also at risk of developing GDM in recurring pregnancies. Factors that increase the risk of GDM in a subsequent pregnancy are hip-to- waist ratio >0.84, weight gain >11 lb (5.0 kg) between pregnancies, and a fat intake >40% of the total calorie intake [80]. Women should be encouraged to adopt healthy lifestyles to lessen their risk of developing type 2 diabetes or GDM in subsequent pregnancies. Recom- mended lifestyle modifications include achieving and maintaining normal body weight, healthy eating habits, and consistent physical activity [61]. 10.12 CONCLUSION Advances in diabetes management have greatly improved pregnancy outcomes. For the woman with preexisting diabetes, optimal maternal blood glucose control must begin before conception and continue throughout the pregnancy. All women with type 1 diabetes and type 2 diabetes of childbearing age should be referred for preconceptional care to incorporate self-management strategies that can decrease perinatal morbidity and mortality. Self-management care includes MNT, self-monitoring of blood glucose, and if necessary, ketone testing, insulin therapy, and physical activity. MNT is a key component in the management of GDM. An individualized meal plan should be designed to provide adequate energy and nutrients for maternal and fetal

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154 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy 75. Jacobson GF, Ramos GA, Ching JY, Kirby RS, R Ferrara A, Field DR (2005) Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization. Am J Obstet Gynecol 193:118–124 76. Conway DL, Gonzales O, Skiver D (2004) Use of glyburide for the treatment of gestational diabetes: the San Antonio experience. J Matern Fetal Med 15:51–55 77. Kjos SL, Henry O, Lee RM, Buchanan TA, Mishell DR (1993) The effect of lactation on glucose and lipid metabolism in women with recent gestational diabetes. Obstet Gynecol 82:451–455 78. Kjos SL, Peters RK, Xiang A, Thomas D, Schaefer U, Buchanan TA (1998) Contraception and the risk of type 2 diabetes mellitus in Latina women with prior gestational diabetes mellitus. J Am Med Assoc 280:533–538 79. Kjos SL (1996) Contraception in diabetic women. Obstet Gynecol Clin North Am 23:243–258 80. Jacob Reichelt AA, Ferraz TM, Rocha Oppermann ML, Costa E, Forti A, Duncan BB, Fleck Pessoa E, Schmidt MI (2002) Detecting glucose intolerance after gestational diabetes: inadequacy of fasting glucose alone and risk associated with gestational diabetes and second trimester waist-hip ratio. Diabe- tologia 45:455–457

11 Preeclampsia Lana K. Wagner, Larry Leeman, and Sarah Gopman Summary Preeclampsia is a multi-organ disease that is specific to pregnancy and is charac- terized by the development of proteinuria and hypertension. It complicates 5–7% of pregnan- cies and specific criteria must be met for diagnosis. The exact etiology or pathophysiology of preeclampsia is poorly understood and as such, there are no well-established methods of primary prevention or of reliable and cost-effective screening. Calcium and aspirin may have a role in preventing preeclampsia in certain subpopulations, and research continues regarding these and other possible nutritional interventions. Preeclampsia is associated with increased maternal mortality and morbidity, and childbirth is the only known cure. Women with preeclampsia need to have regular surveillance. The associated hypertension may war- rant treatment under certain conditions and magnesium sulfate is the drug of choice for the prevention and treatment of eclamptic seizures. Keywords: Preeclampsia, Eclampsia, Hypertensive disorders of pregnancy, Gestational hypertension 11.1 INTRODUCTION Preeclampsia is a multi-organ disease that occurs after 20 weeks gestation and is characterized by the development of proteinuria and hypertension. It is specific to pregnancy and complicates 5–7% of pregnancies [1]. It falls into the larger category of hypertensive disorders of pregnancy, which is addressed briefly within this chapter. The exact etiology or pathophysiology of this disorder is poorly understood. Additionally, there are no well-established methods of primary prevention or of reliable and cost- effective screening. Yet, preeclampsia is associated with increased maternal mortality and morbidity including placental abruption, acute renal failure, cerebrovascular and cardiovascular complications, and disseminated intravascular coagulation [2]. 11.2 HYPERTENSIVE DISORDERS OF PREGNANCY Complications from hypertension are a leading cause of pregnancy-related deaths, ranking third behind hemorrhage and embolism [2]. Hypertensive disorders that may be found during pregnancy include chronic hypertension, preeclampsia– From: Nutrition and Health: Handbook of Nutrition and Pregnancy Edited by: C.J. Lammi-Keefe, S.C. Couch, E.H. Philipson © Humana Press, Totowa, NJ 155

156 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy eclampsia, preeclampsia superimposed on chronic hypertension, and gestational hypertension [3]. Chronic hypertension is hypertension that exists outside of the pregnancy. As such, it will predate the pregnancy, be documented prior to 20 weeks, or will still be present 12 weeks after delivery [3]. Treatment of mild-to-moderate chronic hypertension during pregnancy has not been shown to prevent preeclampsia and has shown no proven fetal benefit [4–6]. Preeclampsia–eclampsia is the onset of hypertension with proteinuria that occurs after 20 weeks of pregnancy. Eclampsia, which occurs in less than one percent of women with preeclampsia [1], is the new onset of seizures during preeclampsia. If a patient has chronic hypertension but develops new or worsened proteinuria, then this is preeclampsia superimposed on chronic hypertension [7]. Also, if there is an acute increase in the hypertension (assuming preexisting proteinuria) or if HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome develops, then this is also considered to be preeclampsia superimposed on chronic hypertension [7]. Gestational hypertension, which used to be known as “pregnancy induced hyper- tension,” [3] is hypertension that develops in the absence of proteinuria. Gestational hypertension develops after 20 weeks of pregnancy and returns to normal within 12 weeks of delivery [7]. 11.3 DIAGNOSIS OF PREECLAMPSIA As mentioned previously, both proteinuria and hypertension after 20 weeks of gestation must be present for a diagnosis of preeclampsia to be made. The diagnostic criteria for preeclampsia are presented in Table 11.1. Blood pressures should be measured with an appropriately sized cuff, with the patient in an upright position [8]. Edema and blood pressure elevations above the patient’s baseline are no longer included in diagnostic criteria [3, 7]. In severe preeclampsia, blood pressures may be higher and proteinuria more pronounced. The diagnostic criteria for severe preeclampsia are also presented in Table 11.1. Any signs or symptoms indicating end organ damage make the diagnosis of severe preeclampsia. Although 24-h urine collections are the gold standard for measuring proteinuria, a random urinary protein-to-creatinine ratio can rule out significant proteinuria if the ratio is less than 0.19 [9]. The urine protein-to-creatinine ratio using the 0.19 cutoff has a sensitivity of 90%, specificity of 70%, and a negative predictive value of 87% [9]. 11.4 PATHOPHYSIOLOGY AND RISK FACTORS The etiology of preeclampsia remains poorly understood. Multiple theories have been proposed regarding the pathophysiology, and no single causal factor has been found [10]. Theories of pathophysiology include genetic predisposition [11–14], abnormal placental implantation [15, 16], angiogenic factors [17], exaggerated inflammatory responses [18], inappropriate endothelial activation [18], vasoconstriction [19], and coagulation cascade defects [19]. Although hypertension and proteinuria are the criteria by which preeclampsia is diagnosed, the pathophysiologic changes associated with preeclampsia affect virtually every organ system. Microthrombi from activation of the coagulation

Chapter 11 / Preeclampsia 157 Table 11.1 Diagnostic Criteria for Preeclampsia and Severe Preeclampsia [3, 7] Preeclampsiaa Severe preeclampsiab Blood pressurec 140 mmHg or higher systolic 160 mmHg or higher systolic Proteinuria 0.3 grams or more in a 24-h urine Or 90 mmHg or higher diastolic (this usually corresponds with 110 mmHg or higher diastolic a 1+ or greater on dipstick) 5 g or more in a 24-h urine Or Other features 3+ or more on two random urine samples collected at least 4 h apart Oliguria (less than 500 ml of urine in 24 h) Cerebral or visual disturbances Pulmonary edema or cyanosis Epigastric or right upper-quadrant pain Impaired liver function Thrombocytopenia Fetal growth restriction a Both hypertension and proteinuria components must be present b One or more must be present in addition to criteria for preeclampsia c Taken on two occasions at least 6 h apart Table 11.2 Risk Factors for Preeclampsia [20] Increased maternal age (>40 years of age) Nulliparity Multiple gestation Preeclampsia in a prior pregnancy Elevated body mass index Certain medical conditions: Chronic hypertension Chronic renal disease Antiphospholipid syndrome Diabetes mellitus cascade, as well as systemic vasospasm, decrease blood flow to organs [19]. Perfusion is further compromised by vascular hemoconcentration and third spacing of intravascular fluids [18]. Risk factors for preeclampsia are presented above in Table 11.2 [20]. Note that young maternal age is no longer considered a risk factor, as this was not supported by a sys- tematic review [20]. Women with preeclampsia should be counseled about the increased risk of recurrent preeclampsia in future pregnancies. The recurrence rate may be as high as 40% in nulliparous women with preeclampsia before 30 weeks gestation and even higher in multiparous women [3].

158 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy 11.5 PREVENTION AND NUTRITION As was stated earlier, there are no well-established methods of primary prevention for preeclampsia, although numerous supplements have been studied regarding their ability to impact its occurrence. Thus far, randomized controlled trials do not support routine prenatal supplementation with magnesium, omega-3 fatty acids, antioxidants (vitamins E and C), or calcium to prevent preeclampsia [21–24]. However, calcium and aspirin may have a role in preventing preeclampsia in certain subpopulations, though the optimal treatment regimens will require further research. Calcium supplementation in high-risk women and in women with low dietary calcium intakes reduced the risk of hypertension and preeclampsia [25]. Also, calcium supple- mentation has been shown to decrease the incidence of neonatal mortality and severe maternal morbidity due to hypertensive disorders when given to normotensive nullipa- rous women [26]. Low-dose aspirin was shown to have small to moderate benefits for prevention of preeclampsia within certain groups of women. A Cochrane analysis demonstrated that in women at increased risk for preeclampsia, 69 women would need to be treated with low-dose aspirin to prevent one case of preeclampsia [27]. However, in the subgroup of women at highest risk for preeclampsia (because of histories of previous severe preeclampsia, diabetes, chronic hypertension, renal disease, or autoimmune disease), only 18 would need to be treated with low-dose aspirin to prevent one case of preeclampsia [27]. Research continues regarding possible nutritional interventions for preeclampsia. While larger studies that are more reliable are needed to confirm results, diets high in fiber and potassium may reduce the risk of preeclampsia [28]. Additionally, diets high in calories, sucrose, and polyunsaturated fatty acids may increase the risk for preeclampsia [29]. 11.6 MANAGEMENT OF PREECLAMPSIA Childbirth is the cure for preeclampsia as the disease process usually resolves within days of delivery. Delivery is always preferable from the perspective of maternal health. However, decisions on induction of labor or cesarean delivery must include a considera- tion of prematurity-related neonatal risks and the severity of the preeclampsia. Women with mild preeclampsia should be carefully followed until they are close to term and delivered at 37–39 weeks [30]. Women with severe preeclampsia may be expectantly managed until 32–34 weeks, or delivered sooner based on maternal and fetal status [31]. Women with preeclampsia need to have regular surveillance of the fetus with nonstress testing and amniotic fluid volume assessment. Blood work should be checked periodi- cally to detect renal or hepatic involvement, hemolysis, or thrombocytopenia. The hypertension of preeclampsia only warrants treatment if the systolic blood pres- sure is above 160 mmHg or the diastolic blood pressure is above 110 mmHg [3]. If these pressures occur near term, then the blood pressure may be managed with intravenous hydralazine or labetalol until delivery [32]. Women with severe preeclampsia undergo- ing expectant management may have their blood pressure controlled with oral labetalol, methyldopa, or nifedipine [3]. Magnesium sulfate is the drug of choice for the preven- tion and treatment of eclamptic seizures [33]. All women with severe preeclampsia need intravenous magnesium in labor and for 24 h postpartum [34]. The use of magnesium

Chapter 11 / Preeclampsia 159 sulfate in women with mild preeclampsia remains controversial, as 400 women may need to be treated to prevent one eclamptic seizure [35]. Neonatal morbidity and mortality is due to the risk of prematurity, uteroplacental insufficiency, or placental abruption. An ultrasound for estimated fetal weight should be done at the time of diagnosis to evaluate for possible intrauterine growth restriction secondary to uteroplacental insufficiency [3]. If delivery is required prior to term, then the birth should occur at an institution with a neonatal intensive care unit capable of caring for infants at the anticipated gestational age. Placental abruption is an unpredict- able event, which can lead to fetal death or morbidity. REFERENCES 1. Witlin AG, Sibai BM (1998) Magnesium sulfate therapy in preeclampsia and eclampsia. Obstet Gyne- col 92:883–889 2. Mackay AP, Berg CJ, Atrash HK (2001) Pregnancy-related mortality from preeclampsia and eclampsia. Obstet Gynecol 97:533–538 3. National Heart Lung and Blood Institute (2000) National High Blood Pressure Education Program Working Group Report on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 183:S1–S22 4. Abalos E, Duley L, Steyn DW, Henderson-Smart DJ (2001) Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev 2 5. Magee LA, Duley L (2003) Oral beta-blockers for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev 3 6. American College of Obstetricians and Gynecologists (2001) ACOG practice bulletin. Chronic hyper- tension in pregnancy, no. 29. Obstet Gynecol 98(Suppl):177–185 7. American College of Obstetricians and Gynecologists (2002) ACOG practice bulletin no. 33: Diagno- sis and management of preeclampsia and eclampsia. Obstet Gynecol 99:159–167 8. US Preventative Services Task Force (1996) Guide to clinical preventative services, 2nd ed,. Williams and Wilkins, Baltimore, Md. Available via http://www.ahrq.gov/clinic/uspstfix.htm 9. Rodriquez-Thompson D, Lieberman ES (2001) Use of a random urinary protein-to-creatinine ratio for the diagnosis of significant proteinuria during pregnancy. Obstet Gynecol 185:808–811 10. Davison JM, Homuth V, Jeyabalan A, Conard KP, Karumanchi SA, Quaggin S, Dechend R, Luft FC (2004) New aspects in the pathophysiology of preeclampsia. J Am Soc Nephrol 15:2440–2448 11. Esplin MS, Fausett MB, Fraser A, Kerber R, Mineau G, Carrillo J, Varner MW (2001) Paternal and maternal components of the predisposition to preeclampsia. N Engl J Med 344:867–872 12. Morgan T, Ward K (1999) New insights into the genetics of pre-eclampsia. Semin Perinatol 23:14–23 13. Lin J, August P (2005) Genetic thrombophilias and preeclampsia: a meta-analysis. Obstet Gynecol 105:182–192 14. Migini LE, Latthe PM, Villar J, Kilby MD, Carroli G, Khan KS (2005) Mapping the theories of preec- lampsia: the role of homocysteine. Obstet Gynecol 105:411–425 15. McMaster MT, Zhou Y, Fisher SJ (2004) Abnormal placentation and the syndrome of preeclampsia. Semin Nephrol 24:540–547 16. Merviel P, Carbillon L, Challier JC, Rabreau M, Beaufils M, Uzan S (2004) Pathophysiology of preec- lampsia: links with implantation disorders. Eur J Obstet Gynecol Reprod Biol 115:134–147 17. Levine RJ, Thadhani R, Quian C, Lam C, Lim KH, Yu KF, Blink AL, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA (2005) Urinary placental growth factor and the risk of preeclampsia. J Am Med Assoc 293:77–85 18. Dekker GA, Sibai BM (1998) Etiology and pathogenesis of preeclampsia: current concepts. Am J Obstet Gynecol 179:1357–1375 19. Roberts JM, Cooper DW (2001) Pathogenesis and genetics of preeclampsia. Lancet 357:53–56 20. Milne F, Redman C, Walker J, Baker P, Bradley J, Cooper C, de Swiet M, Fletcher G, Jokinen M, Murphy D, Nelson-Piercy C, Osgood V, Robson S, Shennan A, Tuffnell A, Twaddle S, Waugh J (2005) The pre-eclampsia community guideline (PRECOG): how to screen for and detect onset of pre- eclampsia in the community. Brit Med J 330:576–580

160 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy 21. Levine RJ, Hauth JC, Curet LB, Sibai BM, Catalano PM, Morris CB, DerSimonian R, Esterlitz JR, Raymond EG, Bild DE, Clemens JD, Cutler JA (1997) Trial of calcium to prevent pre-eclampsia. N Engl J Med 337:69–76 22. Sibai BM, Villar MA, Bray E (1989) Magnesium supplementation during pregnancy: a double blind randomized controlled clinical trial. Am J Obstet Gynecol 161:115–119 23. Salvig JD, Olsen SF, Secher NJ (1996) Effects of fish oil supplementation in late pregnancy on blood pressure: a randomized controlled trial. Br J Obstet Gynaecol 103:529–533 24. Poston L, Briley A, Seed P, Kelly F, Shennan A (2006) Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial. Lancet 367:1145–1154 25. Atallah AN, Hofmeyr GJ, Duley L (2002) Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev 1 26. Villar J, Abdel-Aleem H, Merialdi M, Mathai M, Ali MM, Zavaleta N, Purwar M, Hofeyr J, Nguyen TN, Campodonico L, Landoulsi S, Carroli G, Lindheimer M, (2006) World Health Organization Calcium Supplementation for the Prevention of Preeclampsia Trial Group. Am J Obstet Gynecol. 194:639–649 27. Duley L, Henderson-Smart DJ, Knight M, King JF (2004) Antiplatelet agents for preventing pre- eclampsia and its complications. Cochrane Database Syst Rev 1 28. Frederick IO, Williams MA, Dashow E, Kestin M, Zhang C, Leisenring WM (2005) Dietary fiber, potassium, magnesium and calcium in relation to the risk of preeclampsia. J Reprod Med 50:332–344 29. Clausen T, Slott M, Solvoll K, Drevon CA, Vollset SE, Henriksen T (2001) High intake of energy, sucrose, and polyunsaturated fatty acids is associated with increased risk of preeclampsia. Am J Obstet Gynecol 185:451–458 30. Sibai BM (2003) Diagnosis and management of gestational hypertension and preeclampsia. Obstet Gynecol 102:181–192 31. Churchill D, Duley L (2002) Interventionist versus expectant care for severe pre-eclampsia before term. Cochrane Database Syst Rev 3 32. Duley L, Henderson-Smart DJ (2002) Drugs for treatment of very high blood pressure during preg- nancy. Cochrane Database Syst Rev 4 33. Duley L, Gulmezoglu AM, Henderson-Smart DJ (2003) Magnesium sulfate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev 2 34. The Magpie Trial Collaborate Group (2002) Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomized placebo-controlled trial. Lancet 359:1877–1890 35. Sibai, BM (2004) Magnesium sulfate prophylaxis in preeclampsia: Lessons learned from recent trials. Am J Obstet Gynecol 190:1520–1526

12 AIDS/HIV in Pregnancy Katherine Kunstel Summary Women are among the fastest growing populations of those infected with HIV and AIDS, and most infected women are of childbearing age. Women who are both HIV-positive and pregnant are faced with a double burden both in terms of immunity and nutrition. The HIV-infected pregnant woman is at increased nutritional risk compared to the HIV-uninfected pregnant woman. HIV-infected pregnant women tend to gain less weight during pregnancy. Macronutrient needs are increased to cover the increased demands of both HIV infection and pregnancy and inadequate intake is common. Micro- nutrient deficiencies are also common in HIV-infected pregnant women and can have adverse outcomes for both the mother and the developing child. Other nutrition-related considerations for this population include symptom management, the consequences of antiretroviral therapy, risk of transmission of the virus through breastfeeding, food safety, and food security. Nutrition assessment and counseling is a critical component of the overall care plan for HIV-infected pregnant women. Counseling regarding weight gain, adequate nutrient intake, management of HIV-related symptoms, drug-nutrient interactions, and the risks associated with breastfeeding should be made available to all HIV-infected pregnant women. The nutrition care plan must aim to promote the best outcomes for both the mother and the developing child. Keywords: Nutrition, Pregnancy, HIV, AIDS, Maternal health, Breastfeeding, Pregnancy outcomes 12.1 INTRODUCTION In the United States and Canada, one of the fastest growing populations in the profile of acquired immune deficiency syndrome (AIDS) cases is women [1], and most women who are currently infected with human immunodeficiency virus (HIV) and AIDS are of childbearing age [2]. These facts support the increasing need to consider the implica- tions of HIV and AIDS on pregnancy and lactation. There is no evidence to indicate that pregnancy and lactation have a significant effect on hastening the progression of HIV disease [3, 4]. However, women who are infected with HIV and are pregnant face a double burden in terms of their immune function and face additional potential complica- tions. For example, HIV-infected pregnant women have higher risks of fetal loss [5, 6], From: Nutrition and Health: Handbook of Nutrition and Pregnancy Edited by: C.J. Lammi-Keefe, S.C. Couch, E.H. Philipson © Humana Press, Totowa, NJ 161

162 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy low birth weight, preterm delivery, and intrauterine growth retardation (IUGR) [7]. Additionally, the HIV-infected pregnant woman is at a higher nutritional risk, owing to increased energy needs, tendency to achieve suboptimal weight gain during pregnancy, micronutrient deficiencies, and management of disease symptoms. 12.2 NUTRITIONAL STATUS OF THE MOTHER The nutritional status of an HIV-infected woman prior to and during pregnancy influ- ences both her own health and the health of her unborn child [8]. The nutritional chal- lenges for the HIV-infected pregnant woman are threefold. First, during pregnancy, just as in the uninfected woman, maternal metabolism is altered by hormones in preference of the developing infant, and nutrients are directed to the placenta, the mammary gland, and the infant [9, 10]. Additionally, HIV infection can prompt micronutrient deficiencies and lean body mass depletion because of decreased nutrient intake, malabsorption, and increased utilization and excretion of nutrients resulting in undernutrition [11]. Finally, HIV infec- tion affects nutritional status through an increase in resting energy expenditure (REE) [12–14]. For women who are malnourished, an energy–protein supplement during preg- nancy may improve pregnancy outcomes by improving maternal weight gain and reducing the risk of perinatal mortality [15, 16]. The consequences of maternal malnutrition extend beyond the mother and increase risks for the developing infant as well. For example, poor maternal nutritional status may impair the integrity of the placental lining, creating a more opportune condition for transplacental transmission of HIV [17]. Optimal nutrition during pregnancy increases weight gain and improves pregnancy and birth outcomes [4]. 12.3 WEIGHT GAIN HIV-infected pregnant women tend to gain less weight during pregnancy compared with women who are not infected [4], putting them at higher risk for complications. Additionally, HIV infection is oftentimes associated with wasting and a progressive loss of body mass [18]. This can lead to adverse pregnancy outcomes. Weight loss or sub- optimal weight gain during pregnancy is related to increased risk of intrauterine growth retardation (IUGR) [10], fetal death, preterm delivery, and low-birth-weight (LBW) infants [19, 20]. While overall weight gain is indicative of pregnancy outcomes, Villamor et al. showed that weight loss during the third trimester was more strongly associated with preterm delivery than weight loss during the second trimester, but weight loss during the second trimester was related to an increased risk of fetal death [19]. Weight gain goals during pregnancy for HIV-infected women are the same as those for uninfected women. This weight gain is representative of two entities, the products of conception (fetus, placenta, amniotic fluid) and maternal tissues (expansion of blood and extracellular fluid, uterus, mammary glands, and adipose tissue) [10]. Weight gain goals should be based on the woman’s prepregnancy weight and height [21]. It is recom- mended that a woman with a normal prepregnancy weight for height, or a body mass index (BMI) of 19.8–26 kg/m2 gain approximately 3.5 lb (1.6 kg) in the first trimester and then approximately 1 lb (~0.5 kg) per week during the second and third trimesters, for a total pregnancy weight gain goal of 25–35 lb (11–16 kg). Women who are under- weight for height (BMI < 19.8 kg/m2) prepregnancy should aim to gain approximately 5 lb in the first trimester and a little more than a pound per week in the second and third

Chapter 12 / AIDS/HIV in Pregnancy 163 trimesters, for a total weight gain of 28–40 lb. Women who are overweight for height (BMI > 26–29 kg/m2) prepregnancy should gain approximately 2 lb in the first trimester and slightly less than 1 lb per week in the second and third trimesters, for a total preg- nancy weight gain of 15–25 lb. Obese women (BMI > 29 kg/m2) are recommended to gain at least 15 lb during pregnancy [22] (Table 12.1). 12.4 NUTRIENT NEEDS 12.4.1 Macronutrients HIV infection increases energy needs due to an increase in REE, as previously stated. This increased REE coupled with HIV-related infections and complications, such as anorexia, place HIV-infected pregnant women at greater nutritional risk than the uninfected woman [23, 24]. Current energy recommendations for HIV-infected pregnant and lactating women are an increase of 10% over baseline energy needs during the asymptomatic phase and an increase of 20–30% over baseline energy needs during the symptomatic phase [25]. Early symptomatic HIV infection is defined as the stage of viral infection caused by HIV when symptoms have begun, but before the development of AIDS. Symptoms may include but are not limited to mouth disorders (oral hairy leukoplakia, oral thrush, gingivitis), prolonged diarrhea, swollen lymph glands, prolonged fever, malaise, weight loss, bacterial pneumonia, joint pain, and recurrent herpes zoster. In addition, the World Health Organization (WHO) recommends an intake of an extra 300 kcal per day during all trimesters of pregnancy [26], while the National Research Council recommends an additional intake of 300 kcal per day during the second and third trimesters of pregnancy [27] (Table 12.2). Energy intakes that fall below established recommendations are likely to result in coinciding low intakes of micronutrients such as calcium, magnesium, zinc, vitamin B-6, and folate [19], which have potential consequences for both the mother and developing child. Table 12.1 Recommended Weight Gain for Pregnancy Based on Prepregnancy Weight Underweight BMI (kg/m2) Recommended Normal weight total weight gain (lb) Overweight <19.8 Obese 19.8–26 28–40 (13–18 kg) 26–29 25–35 (11–16 kg) 15–25 (7–11 kg) >29 At least 15 (At least 7 kg) Table 12.2 Adjusted Energy Needs for HIV-Infected Pregnant Women Additional energy Increase in energy needs Plus for pregnancy HIV-asymptomatic pregnant women 10% above normal needs + 300 kcal/day HIV-symptomatic pregnant women 20–30% above normal needs + 300 kcal/day

164 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy Protein requirements are higher during pregnancy to support maternal protein synthesis for expansion of the blood volume, uterus, and breasts and to supply amino acids for synthesis of fetal and placental proteins [27]. The recommended dietary allowance (RDA) for protein for a normal pregnancy and lactation is 71 g per day [28] or approximately 1.1 g/kg/day based on current body weight. This compares to a RDA for protein of 0.8 g/ kg/day for nonpregnant, healthy women [28]. The Institute of Medicine recommends 71 g of protein per day during pregnancy [29]. In the United States and other developed coun- tries, adequate protein intake is not usually a problem. As with nonpregnant individuals, additional protein may be needed under conditions of stress, such as symptomatic HIV infection. However, there is not sufficient data to suggest that HIV infection in and of itself demands a higher protein intake by the infected individual [4]. The Acceptable Macronutrient Distribution Range (AMDR) for fat for normal preg- nancy and lactation is 20–35% of kilocalories for all women from 18 to 50 years of age [28]. Structural and functional changes in the gastrointestinal tract in HIV often affect the absorption of fat, leading to fat malabsorption [16]. In this setting, the use of medium chain triglyceride (MCT) oils may be beneficial. MCT are more easily digested than long-chain triglycerides (LCT) and can be absorbed across the small intestinal mucosa in the absence of pancreatic enzymes [30]. MCT oil can be used as a supplement and added to foods. Also, many enteral feeding formulas designed for patients with fat malabsorption contain MCT oil. 12.4.2 Micronutrients Micronutrient deficiencies are seen more frequently in HIV-infected pregnant women than in HIV-uninfected pregnant women [4]. Deficiencies may be due to physiologic losses, malabsorption, inadequate intake, and lack of knowledge regarding appropriate prenatal nutrition [9]. Poor maternal micronutrient status has consequences for both the mother and the developing infant. Micronutrient deficiencies may result in increased risk for opportunistic infections, more rapid disease progression [31–33], and an increased risk of vertical transmission of the virus as a result of compromised immune status of the mother [17]. Common micronutrient deficiencies that are seen in people with HIV include vitamin A, B-complex, vitamin C, vitamin E, selenium, and zinc, all of which play an important role in immune function and defense against infection [34–37 and Chap. 23, “Micronutrient Status and Pregnancy Outcomes in HIV-Infected Women”]. Iron and folate supplementation is especially important to promote positive pregnancy outcomes, while vitamin A supplementation has been shown to increase the risk of vertical HIV transmission. Zinc deficiency results in reduction of T-cell development and function, affecting immune response [38]. It has also been linked to low-birth-weight outcomes in infected pregnant women. 12.4.3 Iron and Folate During pregnancy, there is an increase in blood volume as a result of expansion of plasma volume by approximately 45–50% and of red cell mass by approximately 15–20% in the third trimester [10]. Anemia is a common condition associated with pregnancy because the expansion of blood cell mass is less relative to plasma, and hemoglobin and hematocrit levels drop as a result [39]. Anemia during pregnancy is associated with complications such as low birth weight, preterm delivery, and increased perinatal mortality

Chapter 12 / AIDS/HIV in Pregnancy 165 [40]. An additional concern for the HIV-infected pregnant woman is bone marrow suppression and hemolysis because of infections; the end result is further depressed hemoglobin [41]. Iron deficiency per se is the prevailing cause of low hemoglobin con- centrations [42], however vitamin A, folate, riboflavin, vitamin B12 [43, 44], and zinc are also essential to erythropoiesis [36]. Folate deficiency causes macrocytic anemia [45] as well as neural tube defects [46] and possibly IUGR and preterm delivery [47]. In a study by Friis et al. [36], HIV was a negative predictor of serum folate, most likely owing to reduced intake and absorption and increased catabolism. The Dietary Reference Intakes (DRI) suggests an intake of 27 mg of iron daily and 600 mcg of folate daily to prevent anemia [48, 49]. WHO recommendations regard- ing supplementation include: 400 mcg of folate and 60 mg of iron daily during the last 6 months of pregnancy to prevent anemia and twice daily doses to prevent severe anemia [50]. The WHO recommendation is most applicable to women who reside in resource-limited settings because it takes into consideration the bioavailability of dietary iron, which tends to be limited in developing countries [9]. There are concerns about potential adverse effects of iron supplementation in the setting of HIV infection [51]. Iron is important for immune function [52] but it also serves as a substrate for enzymes involved in HIV replication [53, 54]. More research is needed to clarify the role of iron in HIV infection before current recommendations regarding intake are reconsidered. 12.4.4 Vitamin A Maternal vitamin A deficiency may cause IUGR and other adverse pregnancy out- comes [55] as well as maternal morbidity and mortality [56]. Additionally, infections may contribute to low vitamin A status in women of reproductive age [57]. In the United States, however, overt vitamin A deficiency is not commonplace [58], and as a fat-solu- ble vitamin, there is the potential for excessive intake in the setting of supplementation. Additionally, in trials conducted in Malawi, South Africa, and Tanzania, Fawzi et al. [59] found that vitamin A supplementation resulted in a significant increased risk of vertical HIV transmission and a significant increase in lower genital viral shedding [60]. Vitamin A supplementation is not recommended for HIV-infected pregnant women. Multivitamin supplementation during pregnancy for the HIV-infected woman has many benefits. Supplementation with a multivitamin (including B-complex, vitamin C, and vitamin E) but not vitamin A alone effectively reduces adverse pregnancy outcomes, such as fetal loss, low birth weight, and prematurity, while also improving maternal weight gain during pregnancy [19, 50]. In addition, micronutrient supplementation has been shown to improve body weight and body cell mass [61], specifically during the last trimester of pregnancy [19, 62], while reducing incidence of opportunistic infec- tions [63] and hospitalizations [64]. Multivitamin supplementation has been shown to significantly decrease the risk of maternal weight loss and also improve hemoglobin concentrations [62]. Fawzi et al. reported that multivitamins had a significant beneficial effect on T-cell subset counts. There were increases seen in both CD4 and CD8 cells, which are the main cellular indicators of immunity in HIV infection [65]. Finally, use of multivitamins or B vitamins and higher dietary intakes of riboflavin, thiamin, and niacin were linked to slower progression of HIV disease [32, 66, 67].

166 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy 12.4.5 Zinc Zinc deficiency has been associated with impaired growth outcomes [68]. In one study of women in the United States with low serum zinc concentrations, there was a signifi- cant increase in fetal growth among the group receiving zinc supplementation [69]. Both the control and supplemented groups received a multivitamin preparation. Results from trials of zinc supplementation in uninfected pregnant women are mixed, and although some benefit has been shown, the data are not conclusive. The RDA for zinc supplementation during pregnancy is 12mg/day for 14- to 19-year- olds and 11 mg/day for women ages 19–50 [49]. However, in developing countries, where there is an increased likelihood of chronic zinc deficiency, prophylactic doses of zinc have been used. The WHO set the Upper Limit (UL) for zinc supplementation at 35 mg/day [70, 29]. 12.5 MEDICATIONS Nutrients and nutritional status of the HIV-infected individual can affect the absorp- tion, use, elimination, and tolerance of antiretroviral medications [71–73]. Treatment of HIV-infected pregnant women is based on the premise that therapies of known benefit to women should not be withheld during pregnancy unless they have known adverse effects on the mother, the fetus, or the infant, and unless the adverse effects outweigh the benefit to the woman [74]. While some antriretroviral mediations are well tolerated, others have potential nutritional side effects. Zidovudine, a nucleoside reverse transcriptase inhibitor (NRTI) that is approved by the US Food and Drug Administration (FDA) for use during pregnancy to prevent vertical transmission of HIV to the newborn is associated with nausea and vomiting, as well as bone marrow suppression that may increase the sever- ity of anemia [16, 23, 75]. Ritonavir, a protease inhibitor (PI) is also associated with gastrointestinal upset, while Indinavir, another PI is associated with hyperbilirubinemia, which is a concern for the newborn [76]. Timing of antiretroviral (ARV) medications with regard to meals is important in terms of medication efficacy and managing drug- related side effects. Indinavir should be taken 1 h before or 2 h after meals [77], but can be taken with light, low-fat meals if necessary. Ritonavir should be taken with food and liquids such as, chocolate milk, to lessen the bitter aftertaste [78] (See Table 12.3). A phenomenon of fat redistribution, or lipodystrophy, is often seen in HIV-infected individuals on ARV therapy, specifically PI, NRTI, or both [79, 80]. This usually occurs as a result of long-term ARV therapy. The syndrome is characterized by loss of sub- cutaneous fat from the face, arms, and legs and oftentimes deposition of excess fat in the neck, upper back, and the trunk [79]. Additionally, metabolic complications such as insulin resistance, hypertriglyceridemia, low levels of serum low density lipoprotein cholesterol, and hyperglycemia are commonly seen. 12.6 SYMPTOM MANAGEMENT Most women who are infected with HIV and become pregnant are asymptomatic [81]. However, for those who are experiencing symptoms, nutritional consequences may occur. Some of the symptoms that may affect nutritional status include anorexia, nausea, vomiting, diarrhea, and chewing and swallowing difficulties [1]. In a study by Kim et al. [82], the clinical symptom that was consistently associated with an inability to meet the RDA for nutrients was anorexia. Reduced intake is an important risk factor for weight

Chapter 12 / AIDS/HIV in Pregnancy 167 Table 12.3 Common Antiretroviral Medications Used During Pregnancy and their Nutritional Effects [74, 75] Possible side effects Administration NRTI Zidovudine Nausea, vomiting, anemia, neutropenia Can be taken with or without food Lamivudine Nausea, vomiting, peripheral neuropathy Can be taken with or without food NNRTI Nevirapine Skin rash (most common) Can be taken with or without food PI Lopinavir/ Diarrhea, headache, nausea, vomiting, Should be taken with food Ritonavir weakness, rash Should be taken with food Nelfinavir Diarrhea, nausea, abdominal pain, dizziness, flatus Should be taken on an empty Indinavir stomach, 1 h before meals or Kidney stones, abdominal pain, 2 h after meals. Can be taken nausea, headache with light, low-fat meal if stomach upset occurs. Ritonavir Nausea, vomiting, diarrhea Should be taken with food or liquids Chocolate milk may help to lessen bitter aftertaste NRTI: nucleoside reverse transcriptase inhibitor; NNRTI: non-nucleoside reverse transcriptase inhibitor; PI: protease inhibitor loss and malnutrition in this population, especially in the setting of opportunistic infections [16]. Strategies for symptom management are outlined in Table 12.4. 12.7 FOOD SAFETY HIV-infected women are more susceptible to bacteria and viruses contaminating food and water [39]. Pregnant, HIV-positive women with negative toxoplasmosis titers should be counseled regarding avoidance of undercooked meats and foods contaminated by soil and animal feces [22]. Food poisoning can lead to weight loss and further compromise immunity to future infections. Proper hand washing, safe food handling and storage, and cooking foods to appropriate temperatures are especially paramount for the safety and health of the HIV-infected pregnant woman. See Table 12.5 for guidelines. 12.8 BREASTFEEDING De Martino et al. [83] report that the risk of mother to child transmission (MTCT) of HIV through breastfeeding ranges from 4 to 14%, depending upon geographic location and whether feeding was sustained for greater than 1 year. Some risk factors for MTCT through breastfeeding include viral load in the blood [84], viral load in breast milk [85], the mother’s immune status [86], the breast health of the mother [87], and the mother’s nutritional status, including hemoglobin and serum retinol levels. [58, 88–89]. Mothers who are HIV-positive should be educated regarding the risks and benefits of different feed- ing options, including the risk of transmitting HIV through breastfeeding [1] as well as

168 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy Table 12.4 Nutrition and Dietary Management of Common HIV Symptoms Anorexia • Eat small, frequent meals. • Capitalize on moments when you are hungry. Keep snacks readily available. • Choose nutrient dense foods (peanut butter, cheese, yogurt). • Avoid foods of low nutrient value (diet foods and beverages). Nausea and vomiting • Keep something in your stomach to curb nausea (i.e. crackers). • Choose bland foods that are easy to digest such as toast, pasta, oatmeal, turkey, and pudding. • Avoid greasy, high fat foods. • Avoid spicy or highly seasoned foods. Diarrhea • Select binding foods such as bananas, toast, rice, and applesauce. • Avoid high fat foods and lactose-containing foods. • Drink adequate fluids to replace losses (water, sports drink, juices). Sore mouth and throat • Select smooth textured foods, such as pudding, yogurt, scrambled eggs, bananas, and applesauce. • Avoid foods that are acidic, spicy, and that have rough edges and textures. • Add moisture to foods with broths and gravies. • Use a straw to drink liquids. Table 12.5 Guidelines for Food Safety • Ensure proper hand washing. • Handle and store food in a safe manner (i.e. separate raw foods from prepared foods). • Cook foods to appropriate temperatures. • Store and keep foods at appropriate temperatures. • Avoid raw or undercooked potentially hazardous foods (i.e. meat, poultry, fish, eggs). • Use water from a clean and safe water supply. an increased mortality rate among HIV-infected pregnant women who breastfeed [90]. The metabolic demands of lactation as well as the metabolic demands of HIV infection are thought to lead to nutritional impairment and subsequently, an increased risk of infant mortality [90]. It is recommended that mothers who can provide an alternate feeding method that is acceptable, affordable, sustainable, and safe are advised to do so [91]. The Centers for Disease Control and Prevention (CDC) recommend that HIV-infected pregnant women in the United States avoid breastfeeding [92]. For those mothers who choose to breastfeed, the quality of the breast milk is linked to the nutritional status of the mother, specifically the concentrations of both macronutrients and micronutrients as well as immunologic properties [17]. Mixed feeding, which is

Chapter 12 / AIDS/HIV in Pregnancy 169 defined as breastfeeding coupled with other foods and liquids by mouth, appears to add to transmission risk in the first 6 months of life [93]. Longer durations of breastfeeding by HIV-infected mothers are associated with an increased risk of HIV transmission to their infants and early weaning from human milk (i.e., at 6 months of age) is recom- mended to limit the child’s exposure to HIV-infected human milk [90]. 12.9 GOALS OF NUTRITION CARE The following goals for maternal nutritional care have been outlined by Lwanga [94]: 1. Improve nutritional status, maintain weight, prevent weight loss, and preserve lean body mass. 2. Ensure adequate weight gain during pregnancy. 3. Ensure adequate nutrient intake by improving dietary habits and encouraging appropriate macronutrient and micronutrient intake. 4. Prevent foodborne illness by promoting food and water safety. 5. Manage symptoms that affect nutrient intake to minimize the impact of secondary infec- tions on nutritional status. The general goal of nutritional assessment and interventions is to improve nutritional status, enhance quality of life, and prolong the survival of the mother [95]. 12.10 APPROACHES TO NUTRITIONAL CARE The following is a recommended approach to nutritional care for the HIV-infected pregnant woman and includes a baseline nutritional assessment, nutritional counseling, and follow-up nutritional care. 12.10.1 Nutritional Assessment A baseline assessment should be made at the first prenatal visit and follow-up care should be provided at subsequent visits. The initial nutritional assessment should include base- line anthropometric measurement such as weight, height, BMI (height [cm]/kg [m2]), and mid–upper arm circumference (MUAC) [23]. The BMI will indicate whether the woman is at an appropriate weight or is underweight or overweight at onset of pregnancy. This infor- mation will enable the provider to make specific weight gain recommendations and allow for tracking of weight gain during pregnancy. Additionally, women who have a MUAC of <23cm are at even greater nutritional risk [96, 97]; thus, this anthropometric marker may indicate the need for more aggressive nutritional intervention. Biochemical assessment measures including serum albumin, transferrin, hematocrit, creatinine, urea nitrogen, lipids, and micronutrients indicate disease prognosis and potential complications [98, 99]. These markers should be included in the initial assessment and followed throughout pregnancy. The initial assessment takes into account the diet history of the woman as well as any symptoms or problems that might hinder adequate intake. Typical dietary, appetite, gastrointestinal symptoms (i.e., nausea, vomiting, diarrhea, and constipation), difficulty with chewing and swallowing, food allergies, ethnic and cultural food practices, and household food security should be considered and included in the assessment. Further- more, all medications and supplements as well as complementary therapies should be investigated in order to determine possible drug-nutrient interactions.

170 Part II / Nutrient Needs and Factors Related to High-Risk Pregnancy 12.10.2 Nutritional Counseling Weight gain goals should be set based on the woman’s BMI at baseline. If underweight (BMI < 19.8 kg/m2), then she needs to gain 28–40 lb during pregnancy. If at appropriate weight (BMI 19.8 – 26 kg/m2), then she needs to gain 25–35 lb during pregnancy. If over- weight (BMI > 26–29 kg/m2), then she needs to gain 15–25 lb during pregnancy. If obese (BMI > 29kg/m2), then she needs to gain at least 15lb during pregnancy (refer to Table 12.1). Energy needs are dependent on whether the woman is asymptomatic or symptomatic at the time of assessment. If asymptomatic, then her calorie needs are increased by 10% plus an additional 300 kcal per day on average during pregnancy (500 kcal per day during lactation). (see Chaps. 1 and 18, “Nutrient Recommendations and Dietary Guidelines for Pregnanat Women” and “Nutrition Issues During Lactation”). If symptomatic, then her calorie needs are increased by 20–30% plus an additional 300 kcal per day during preg- nancy (500 kcal per day during lactation). Protein needs are estimated to be approximately 1 g/kg/day. Encourage a diet that is nutritionally adequate and varied. Additional multivitamin and min- eral supplementation is also encouraged. Specific nutrients of importance are iron and folate. The DRI for iron is 27 mg/day and for folate is 600 mcg per day. While prenatal vitamins vary, most provide approximately 800–1,000 mcg of folic acid and 30 mg of iron per dose. Provide counseling regarding breastfeeding and risk of MTCT of HIV. Address food safety with regard to proper hand washing, safe food handling and storage, and safe cooking temperatures. Provide counseling for women on ARV treatment regarding meal planning, symptom management, and the metabolic changes associated with ARV therapy. 12.11 CONCLUSION Nutrition assessment and counseling are critical components of the care plan for HIV-infected pregnant women. The compounding effects of pregnancy and HIV-infec- tion place HIV-infected pregnant women at greater nutritional risk. Adequate weight gain and nutrient intake and symptom management are especially challenging for this population. Intervention in terms of care for HIV-infected pregnant women tends to be directed towards pregnancy outcomes and fetal health, more so than to maternal health and maternal morbidity and mortality. Given the growing population of HIV-infected women of childbearing age, there is a need for more research to determine the best nutrition and medical care plans for promoting both maternal and fetal health. REFERENCES 1. American Dietetic Association and Dietitians of Canada (2004) Position of the American Dietetic Association and Dietitians of Canada: nutrition intervention in the care of persons with human immu- nodeficiency virus infection. J Am Diet Assoc 104:1425–1440 2. Seguardo AC, Miranda SD, Latorre M (2003) Evaluation of the care of women living with HIV/AIDS in Sao Paulo, Brazil. AIDS Patient Care and STDs 17:85–93 3. Tinkle MB, Amaya MA, Tamayo OW (1992) HIV disease and pregnancy, Part 1. Epidemiology, patho- genesis, and natural history. J Obstet Gynecol Nurs 21:86–93 4. World Health Organization (2005) Nutrition and HIV/AIDS: Report by the secretariat, Geneva, Swit- zerland, 12 May 2005 5. Gray RH, Wawer MJ, Serwadda et al (1998) Population-based study of women with HIV-1 infection in Uganda. Lancet 351:98–103

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Part III: Special Diets, Supplements, and Specific Nutrients During Pregnancy



13 Popular Diets Nancy Rodriguez and Michelle Price Judge Summary Popular diets are a constant in the lives of women. And while some restricted- calorie plans recommending extreme differences in the contribution of calories from fat, carbohydrate, and protein may promote weight loss in some women, they should not be undertaken during pregnancy. Unfortunately, the scientific literature documenting the prevalence of use of popular diets in pregnant women, or more importantly the effects of such dietary behavior on pregnancy outcomes, is, for all practical purposes, nonexistent. Energy balance is central to the regulation of body weight. During pregnancy, the intent is for energy balance to be positive such that fetal growth and development is well supported by adequate calories and essential nutrients. The coexistence of a state of negative energy balance for the purpose of weight loss during pregnancy will not sup- port optimal gestation. An appreciation of the basic principles of the most established popular diets in the context of nutrition and pregnancy will provide a foundation for the clinician and other healthcare professionals who treat and counsel pregnant women and women of childbearing age. This chapter provides a framework for practitioners from which thoughtful and appropriate discussions can result when approached with ques- tions regarding the potential concerns associated with the practice of such diet behaviors during pregnancy. Without question, the best approach to healthful weight management during pregnancy combines a well-balanced diet with reasonable, routine physical activity and exercise. Habitual consumption of a well planned, energy sufficient diet containing the recommended amount of the macro- and micronutrients for the duration of pregnancy will minimize weight-related issues and other metabolic problems from conception to delivery. Clinicians and practitioners should be familiar with the premise of popular diets so they are prepared to offer appropriate counsel when they encounter dieting behaviors during their patients pregnancy. Keywords: Popular diets, Weight management, exercise, pregnancy 13.1 INTRODUCTION Women are most susceptible to the seduction of weight loss promised by the over- whelming number of popular diets promoted by the media. Although essentially no scientific literature documenting the prevalence of use of popular diets in pregnant women exists, clinicians and practitioners should be familiar with the premise of these From: Nutrition and Health: Handbook of Nutrition and Pregnancy Edited by: C.J. Lammi-Keefe, S.C. Couch, E.H. Philipson © Humana Press, Totowa, NJ 177

178 Part III / Special Diets, Supplements, and Specific Nutrients During Pregnancy diets in the event they encounter dieting behaviors during pregnancy in their patients. This chapter highlights the basic principles of the most established popular diets in the context of nutrition and pregnancy to provide a foundation for the clinician and other healthcare professionals who treat and counsel pregnant women and women of child- bearing age. The intent is not to promote the use of popular diets by these women, but to provide a foundation for practitioners from which thoughtful and appropriate discus- sions can result when approached with questions regarding whether such diet behaviors are appropriate during pregnancy. Although less enticing, the best approach to healthful weight management during pregnancy combines a well-balanced diet with reasonable, as well as routine, physical activity and exercise. A well-planned diet that provides ade- quate energy and meets macronutrient and micronutrient requirements for the duration of pregnancy is the basis for minimizing weight-related issues and other metabolic prob- lems from conception to delivery. Because energy balance (i.e., energy in and energy out), as well as diet composition (i.e., percent of calories provided by carbohydrate, pro- tein and fat), is central to the discussion of popular diets, points specific to contemporary diet plans are integrated throughout the chapter. 13.2 RECOMMENDATIONS FOR WEIGHT GAIN DURING PREGNANCY Guidelines for weight gain during pregnancy aim to promote adequate, but not exces- sive, weight gain for optimal fetal development. Weight gain is highly correlated with infant birth weight making optimal weight gain during pregnancy important to fetal out- comes [1]. For a thorough discussion of optimal weight gain for pregnancy, the reader is referred to Chap. 2, “Optimal Weight Gain,” in Part 1 of this book. In brief, the Institute of Medicine (IOM) developed guidelines for maternal weight gain based on aggregate data examining fetal outcomes and associated maternal conditions [1]. These guidelines, adapted by both the American College of Obstetrics and Gynecology (ACOG) and the American Dietetic Association (ADA), use maternal body mass index (BMI, kg/m2) prior to conception (Tables 13.1, 13.2) as a starting point for recommended weight gain during pregnancy [1–4]. Although these guidelines are available to women during preg- nancy, educational programs regarding how to follow these guidelines appear to be lacking as evidenced by several studies documenting that only 30–40% of American women meet the IOM guidelines for weight gain [1, 3]. Table 13.1 ACOG Guidelines for Weight Gain during Pregnancy [1] Condition prior to pregnancy Weight gain guideline (lb) Underweight 28–40 (12.7–18.2 kg) Normal weight 25–35 (11.4–16 kg) Overweight 15–25 (6.8–11.4) Obese 15 (6.8 kg) Twins/triplets 35–45 (16–20.5 kg)

Chapter 13 / Popular Diets 179 Table 13.2 ADA Position Paper: Guidelines for Weight Gain during Pregnancy Body mass index (BMI) Recommended weight gain Weight gain/week after 12 weeks 0.5 kg (1 lb) BMI <19.8 12.5–18 kg (28–40 lb) 0.4 kg (0.9 lb) BMI 19.8–26 11.5–16 kg (25–35 lb) 0.3 kg (0.7 lb) BMI > 26–29 7–11.5 kg (15–25 lb) BMI > 29 At least 7 kg (15 lb) 0.7 kg (1.5 lb) Twin pregnancy 15.9–20.4 kg (34–45 lb) Triplet pregnancy Overall gain of 22.7 kg (50 lb) While managing a healthy weight throughout pregnancy may be a challenge for many women, it is important for women to embrace the fact that they are pregnant and need to gain weight in order to ensure having a healthy baby. Weight reduction during preg- nancy is discouraged and has been associated with neuropsychological abnormalities and low birth weight in the infant [2]. Conversely, excess weight gain can place women at higher risk for complications. Women should not use pregnancy as an excuse to eat excessively. Although diet is a key component to weight maintenance, exercise, rest, and lifestyle are also highly important. During pregnancy, women should strive to eat a varied diet that encompasses all of the nutrients essential for fetal development. This varied diet should be well balanced and not too high or low in any one of the macronutrients. 13.3 RECOMMENDATIONS FOR HEALTHY EATING A complete approach to meeting nutrient and health needs during normal pregnancy is presented in Part 1 of this book. Specific aspects of this information in the context of weight management are presented here. 13.3.1 Energy Activity level, age, height, and weight prior to pregnancy are all factors that are considered when determining an individual’s energy requirements. Although energy requirements vary from woman to woman, most women’s energy needs range from approximately 2,500 to 2,700 kcal daily [4]. Caloric requirements during the second and third trimesters of pregnancy are estimated to be 300 kcal/day (500 kcal/day for adolescents <14 years of age) above caloric requirements prior to pregnancy. The prepregnancy energy requirements used as a basis for this caloric estimation during pregnancy should account for age, activity level, and prepregnancy weight [4]. The Dietary Reference Intakes (DRIs) for pregnancy take into account increasing needs in support of fetal growth and appropriate maternal weight gain [5–7]. Butte and King [8] estimated energy costs of pregnancy using respiratory calorimetry throughout pregnancy and found that the daily cost of pregnancy increased by trimester. Weight gain during pregnancy should be individualized relative to prepregnancy BMI such that pregnancy outcome is improved, postpartum weight retention is minimized, and risk for adult chronic disease is reduced in the child [1]. In special situations such as adolescent pregnancy in which additional calories are necessary for the adolescent’s

180 Part III / Special Diets, Supplements, and Specific Nutrients During Pregnancy own growth energy, requirements may be higher to maintain weight gain goals [2]. Pregnant adolescents less than 14 years of age require an additional 500 kcal/day [4, 9]. Likewise, women carrying twins need to consume 500 calories daily above energy needs for pregnancy as outlined above [7, 10]. Conversely, women who are over- weight or obese prior to pregnancy will require fewer calories due to the availability of stored energy. In any case, it is important that positive energy balance (energy in vs. energy out) exists such that a pregnant woman is in an anabolic state (energy in > energy out). The degree of positive energy balance should be determined relative to an individual woman’s prepregnancy body weight (Tables 13.1, 13.2). Theoretically, an overweight woman may eat fewer calories when she becomes pregnant but still achieve an anabolic state because the degree of positive energy balance (calorie intake in excess of energy expended), while less than that prior to the pregnancy will gener- ally be sufficient to support fetal growth and development. Once energy needs are established, it is important that the pregnant woman under- stands how to translate her calorie needs into appropriate food choices to support a healthy pregnancy. Requirements for some nutrients, such as protein, iron, and calcium, are increased during pregnancy. Therefore, pregnant women should focus on nutrient dense foods [foods that provide a lot of nutrients relative to the number of calories]. For example, one egg will contribute high-quality protein, essential fat, as well as a variety of vitamins and minerals, for approximately 75 calories. Too often patients are given calorie levels that may be specific to their needs without adequate instruction on how to incorporate these guidelines into their daily routines. Twenty-four-hour diet recalls con- ducted and evaluated by a registered dietitian, in combination with appropriate nutrition education materials, can be very useful in assisting the individual in translating their usual diet into meal plans that are consistent with recommendations for appropriate and healthy weight gain throughout pregnancy. 13.3.2 Diet Composition The amount of energy contributed by the macronutrients—carbohydrate, protein, and fat—does not vary substantially during normal pregnancy. The role of each of these nutrients in normal physiology and metabolism remains intact with a heightened impor- tance for some functions in the context of fetal growth and development. For that reason, it is critical that pregnant women do not self-impose diet restrictions or extremes during pregnancy. 13.3.2.1 Carbohydrate Carbohydrate is the brain’s main fuel and the nutrient that fuels muscles for daily tasks and exercise. The growing fetus relies on the mother’s carbohydrate supply. A diet too low in carbohydrate can affect the energy level of the mother. During normal pregnancy, care should be taken to ensure that 50–60% of daily calories are provided as carbohydrate. Diets low in carbohydrate should not be attempted during pregnancy, as the effects of such a diet on fetal development are not known. Carbohydrate source should be well planned to ensure that the majority of carbohydrates are complex, with a limited consumption of refined sugar or simple carbohydrate. Examples of complex carbohydrates include bread, rice, beans, pasta, and potatoes. When grains are refined, they are stripped of many important nutrients, including fiber, which are important in

Chapter 13 / Popular Diets 181 pregnancy. Pregnant women should be advised to consume whole-grain bread, cereal, and pasta products. Fruits, vegetables, and whole-grain products are good sources of dietary fiber that are beneficial in preventing constipation during pregnancy. Foods with simple sugar like candy, soft drinks, and desserts should be limited during pregnancy as they are high in calories and low in nutritional value. These fat and sugar-laden foods can displace other more nutritious foods and contribute to accelerated weight gain. A woman requiring 2,500 kcal daily would need 275–330 g of carbohydrate daily. One slice of bread, 1/2 cup of cooked pasta, 1/2 cup dry cereal or a serving of fruit all provide ~15 g of carbohydrate per serving. 13.3.2.2 Protein Adequate protein intake during pregnancy is important to maintain maternal health during pregnancy as well as provide important building blocks for fetal growth and development. Protein provides the structural framework for the body, is integral to the immune system, transports substances throughout the body, is the basis for many hor- mones and enzymes, and maintains fluid balance. Pregnant women need a minimum of 60 g of protein daily [2]. Good sources of dietary protein include meat, poultry, fish, dairy products, legumes, beans, and nuts. One ounce of meat, poultry, fish, or cheese provides 7 g of protein. One 8-oz. glass of skim milk provides 9 g of protein. Two 3-oz. servings of meat, poultry, or fish and three 8-oz glasses of milk will provide the protein necessary to meet the protein needs of pregnancy. 13.3.2.3 Fat Fat is more energy dense than carbohydrate or protein (9 kcal/g vs. 4 kcal/g for fat and carbohydrate and protein, respectively) when consumed within recommended guidelines, fat is beneficial to maternal health and fetal development. Fats are important in maintain- ing skin health, as a structural component of cells, for absorption of vitamins A, D, E, and K as regulatory messengers (hormones), hormone, and for immune function. Recent evidence suggests that omega-3 fatty acids consumed during pregnancy are beneficial to cognitive development in infancy and childhood [11–14]. Pregnant women should con- sume 25–30% of their daily energy as fatty acids. A woman requiring 2,500 kcal/day would need to consume 69–83 total grams of fats daily. These fat requirements should be met using vegetable-based oils made up of unsaturated fat rather than animal and plant- based saturated fats that can be more problematic to health [15]. Sources of unsaturated fats include olive oil, canola oil, peanut oil, sunflower oil, flax seed oil, and fish oil. Canola oil and flax seed oil are sources of the essential fatty acid α-linolenic acid. Dietary oils either derived or obtained directly from fish are particularly beneficial during pregnancy as fish contains a preformed source of docosahexaenoic acid (DHA) which is the metabolic end product of α-linolenic acid in the body [16] and pref- erentially transferred to fetal tissue during pregnancy [17–19]. Women should consume 300 mg of DHA daily during pregnancy [20]. Many pregnant women are concerned about eating fish during pregnancy due to potential contamination; however, women need to be educated about safe fish intake during pregnancy to ensure consumption of these impor- tant omega-3 fatty acids (http://www.cfsan.fda.gov/~comm/haccp4.html). Omega-6 fatty (linoleic) acid should make up 2% of total energy during pregnancy. This recommendation does not differ from the recommendation for the general adult population [20].

182 Part III / Special Diets, Supplements, and Specific Nutrients During Pregnancy Table 13.3 Micronutrient Deficiency Risks Associated with Various Popular Diets Popular diet type: Micronutrient Fat restrictive Fat soluble vitamins (A, D, E, K), essential fatty acids Protein restrictive Iron, vitamin B12, zinc, magnesium, essential amino acids Non-dairy Calcium, vitamin D Carbohydrate restrictive B vitamins, vitamins C, A, K and D, potassium, fiber Sources of saturated fat include whole milk, beef, cheese, lard, shortening, and palm and coconut oil. No more than 10% of daily calories should come from a saturated fat source. A woman who requires 2,200 kcal daily should consume no more than 24 g of saturated fat daily. 13.3.3 Micronutrients Pregnancy is a time to ensure adequate micronutrient intake in addition to sufficient energy and macronutrients for optimal fetal development. The key to ensuring dietary adequacy of the micronutrients is a varied diet that includes multiple foods from all food groups. Factors that place pregnant women at risk for micronutrient deficiencies include diets that restrict energy, diets that omit one or more major food groups, food insecurity, food intolerances, allergy or food aversions. Dietary plans should be devel- oped according to risk factors that include alternative dietary sources. Attention should also be given to potential micronutrient deficiencies associated with the respective types of diets. Several micronutrients are of critical importance to the fetus’s growth and development (Table 13.3). 13.4 ACCEPTABLE PHYSICAL ACTIVITY AND EXERCISE PLANS A plan for regular exercise is another key component of weight management [21–25]. Women need to dispel the myth that women should “take it easy” during pregnancy. Chapter 3, “Physical Activity and Exercise in Pregnancy,” provides a thorough dis- cussion regarding physical activity and exercise during pregnancy. In brief, pregnant women should consult their doctor before initiating an exercise program or modifying their existing regimen to rule out complications [24]. Light-to-moderate physical activity does not negatively influence fetal development for a normal, uncomplicated pregnancy [21, 25]. A properly designed exercise program during pregnancy is beneficial and can contribute to healthy weight management at this time [22, 24]. In addition to adequate calorie and nutrient intake, and appropriate exercise and physical activity, various lifestyle factors should be considered when planning for appropriate weight gain during pregnancy. Occupation, leisure activities, stress level, and habitual dietary behaviors (i.e., eating out, eating cues, binge eating) are important considerations for weight management programs. Behavior modification strategies may need to be implemented for women who have problems with habitual unhealthy dietary behaviors (See Chap. 9, “Anorexia Nervosa and Bulimia Nervosa during Pregnancy”). All of these factors should be taken into consideration in consultation with a registered dietitian and in collaboration with the supervising physician.

Chapter 13 / Popular Diets 183 13.5 POPULAR DIETS: IMPLICATIONS FOR PREGNANCY In general, it is important for women to understand that the goal during pregnancy is a healthy baby and not weight loss. Pregnant women should not fall prey to fad diets or diet plans that limit the types of foods that can be eaten. With the ongoing exposure to the written and visual media directed at body image, it is not surprising that some pregnant women might become fearful of weight gain during pregnancy and consider very meticu- lous and restricted eating plans. These plans are likely to parallel the popular diets being marketed at the time. The challenge to practitioners is to stay abreast of current diet trends so they are prepared to educate women regarding potential pitfalls of these weight loss plans specific to pregnancy. Fortunately for doctors, nurses, dietitians, and other allied health professionals working with pregnant women, the principles and recommendations for healthy weight gain during pregnancy are straightforward allowing for easy identifica- tion of nutrient- or metabolic-specific flaws of popular diets in the context of pregnancy. In addition, although not particularly seductive, the most effective approach to weight management is based on the simplicity of weight management: energy balance. To gain weight, energy intake must exceed that expended so the body is able to invest energy in the anabolic reactions critical to the deposition of musculoskeletal tissues and the devel- opment of organs and the nervous system. Weight loss or maintenance will occur when energy intake is less than or equal to that expended, respectively. Popular diets typically lead the consumer away from this concept with false promises most often based on changes in the composition of the calories eaten, rather than the total amount of calories consumed relative to what is needed. Weight management plans focusing on the macronutrient composition of the diet have become the cornerstone of popular diets most likely to be considered by a pregnant woman. Plans that reduce carbohydrate intake in exchange for increasing protein and fat may be particularly troublesome during pregnancy [26, 27]. The following discussion addresses various versions of popular diets that practitioners working with pregnant women may encounter. Because the scientific literature is essentially void of research in this area, points are made within the context of what is known regarding optimal nutrition for a healthy pregnancy and how these particular diet practices might undermine these recommendations. 13.5.1 Low-Carbohydrate Diets Low-carbohydrate diets are perhaps the most prolific of all weight loss plans. In 1992, Dr. Robert Atkins published Dr. Atkins’ New Diet Revolution [28]. This was eventu- ally followed by the publication of two subsequently revised versions of the book. The premise of this plan is to restrict carbohydrate intake so severely that ketoacidosis ensues. The plan, which provides only 20 g of carbohydrate during the “Induction Phase,” allows for extremely high-fat (particularly saturated fat) and protein intakes [28] relative to what is generally recommended as healthful for the general population [29]. It should be readily apparent to the practitioner that this amount of carbohydrate is inadequate for supporting pregnancy [1, 6, 29, 30]. More importantly, a state of ketosis during pregnancy is not con- sistent with a normal metabolic profile for gestation and can be problematic for both the mother and fetus [26, 31]. In addition, the amount of calories that is ultimately provided by this plan will not meet the energy needs of pregnancy.

184 Part III / Special Diets, Supplements, and Specific Nutrients During Pregnancy The immediate physiological response to the Atkins diet is a significant weight loss within 7–10 days of following the diet plan. A large component of weight loss is due to fluid losses that are associated with ketosis and needed for excretion of nitrogenous metabolites consequent to excessive dietary protein. Neither of these scenarios is desirable for the pregnant woman. β-Hydroxybutyrate has been shown to cross the placenta in high amounts in sheep and produce significant decreases in fetal oxygenation, lactate, and fetal heart rate [32]. Although it is currently unknown how ketoacidosis impacts fetal outcome, in human, pregnancy complicated with diabetes places the developing fetus at risk for spontane- ous abortion, stillbirth, congenital malformation, and macrosomia [33]. Given these negative outcomes associated with uncontrolled diabetes during pregnancy and subsequent ketoacidosis, women should avoid ketogenic diets during pregnancy. Normal hydration is important for body functions and physical performance and concerns regarding the impact of excessive nitrogen secretion on renal function remain an issue for healthy men and nonpregnant women [34, 35]. Although various studies have been published to document potential benefits of the Atkins Diet to reducing risk factors for cardiovascular disease [36], there remains absolutely no premise for induc- tion of ketosis during pregnancy. Even Dr. Atkins himself warned that his diet is not an appropriate eating plan for pregnancy [28]. The public’s fascination with the resurgence of the Atkins diet in the twentieth century resulted in the publication of two other books that promoted higher protein intakes for weight loss, The Zone Diet and The South Beach Diet [37, 38]. These books exploited the concept of high-protein intakes for the purpose of weight loss. However, these higher protein intakes are not at levels that carbohydrate intake is restricted to the extent that ketosis occurs. Rather, these plans intended to slightly exceed recommended protein intakes for maintaining muscle mass during weight loss, keep fat within recommended ranges of approximately 30% of total calories, and promote a level of carbohydrate intake that prevents extreme fluctuations in blood glucose thereby keeping insulin secretion at bay [37, 38]. The drawback to these plans was the lack of controlled scientific studies in support of this approach to weight management. However, both authors do an exceptional job reviewing and distilling the existing scientific literature in developing the hypotheses for their respec- tive weight loss programs. As a result, the arguments presented, along with the anectodal reports of successful weight loss efforts sustained the popularity of these approaches to weight management. Eventually the scientific community was challenged to design and execute investigations that would either support or refute claims put forth by these weight loss programs. And indeed, it would appear that reduced calorie diets for which protein intakes are slightly above the recommended amount (1.5 g/kg vs. 0.8 g/kg) are quite effec- tive in eliciting weight loss when combined with regular exercise [23, 39–42]. Of significance to this chapter, however, is that this work was carried out in healthy, overweight men and women, not pregnant women. An evidence-based analysis by the Cochrane group documented that balanced energy and protein intakes as recommended for pregnancy are an appropriate guide for normal, healthy fetal growth and develop- ment [43]. The report further states, “high-protein or balanced-protein supplementation alone is not beneficial and may be harmful to the fetus” [43]. That is, protein intakes in excess of the current RDA for pregnancy are of no benefit during pregnancy and may